Rhodopsin-like receptors (class A/1) are the largest group of GPCRs and are the best studied group from a functional and structural point of view. They show great diversity at the sequence level and thus, can be subdivided into 19 subfamilies (Subfamily A1-19) based on a phylogenetic analysis (Joost P and Methner A, 2002). They represent members which include hormone, light and neurotransmitter receptors and encompass a wide range of functions including many autocrine, paracrine and endocrine processes.
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Wellendorph P, Goodman MW, Burstein ES, Nash NR, Brann MR, Weiner DM.; ''Molecular cloning and pharmacology of functionally distinct isoforms of the human histamine H(3) receptor.''; PubMedEurope PMCScholia
Torricelli M, Giovannelli A, Leucci E, Florio P, De Falco G, Torres PB, Reis FM, Leoncini L, Petraglia F.; ''Placental neurokinin B mRNA expression increases at preterm labor.''; PubMedEurope PMCScholia
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Tatemoto K, Hosoya M, Habata Y, Fujii R, Kakegawa T, Zou MX, Kawamata Y, Fukusumi S, Hinuma S, Kitada C, Kurokawa T, Onda H, Fujino M.; ''Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor.''; PubMedEurope PMCScholia
Lee MJ, Evans M, Hla T.; ''The inducible G protein-coupled receptor edg-1 signals via the G(i)/mitogen-activated protein kinase pathway.''; PubMedEurope PMCScholia
Combadiere C, Ahuja SK, Murphy PM.; ''Cloning and functional expression of a human eosinophil CC chemokine receptor.''; PubMedEurope PMCScholia
Chaudhuri A, Polyakova J, Zbrzezna V, Williams K, Gulati S, Pogo AO.; ''Cloning of glycoprotein D cDNA, which encodes the major subunit of the Duffy blood group system and the receptor for the Plasmodium vivax malaria parasite.''; PubMedEurope PMCScholia
Nylander S, Femia EA, Scavone M, Berntsson P, Asztély AK, Nelander K, Löfgren L, Nilsson RG, Cattaneo M.; ''Ticagrelor inhibits human platelet aggregation via adenosine in addition to P2Y12 antagonism.''; PubMedEurope PMCScholia
Wangler NJ, Jayaraman S, Zhu R, Mechref Y, Abbruscato TJ, Bickel U, Karamyan VT.; ''Preparation and preliminary characterization of recombinant neurolysin for in vivo studies.''; PubMedEurope PMCScholia
Deo DD, Bazan NG, Hunt JD.; ''Activation of platelet-activating factor receptor-coupled G alpha q leads to stimulation of Src and focal adhesion kinase via two separate pathways in human umbilical vein endothelial cells.''; PubMedEurope PMCScholia
Tsuzuki S, Ichiki T, Nakakubo H, Kitami Y, Guo DF, Shirai H, Inagami T.; ''Molecular cloning and expression of the gene encoding human angiotensin II type 2 receptor.''; PubMedEurope PMCScholia
Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L, Daniels D, Muir AI, Wigglesworth MJ, Kinghorn I, Fraser NJ, Pike NB, Strum JC, Steplewski KM, Murdock PR, Holder JC, Marshall FH, Szekeres PG, Wilson S, Ignar DM, Foord SM, Wise A, Dowell SJ.; ''The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids.''; PubMedEurope PMCScholia
Fricks IP, Carter RL, Lazarowski ER, Harden TK.; ''Gi-dependent cell signaling responses of the human P2Y14 receptor in model cell systems.''; PubMedEurope PMCScholia
Wang W, Soto H, Oldham ER, Buchanan ME, Homey B, Catron D, Jenkins N, Copeland NG, Gilbert DJ, Nguyen N, Abrams J, Kershenovich D, Smith K, McClanahan T, Vicari AP, Zlotnik A.; ''Identification of a novel chemokine (CCL28), which binds CCR10 (GPR2).''; PubMedEurope PMCScholia
Rodriguez M, Beauverger P, Naime I, Rique H, Ouvry C, Souchaud S, Dromaint S, Nagel N, Suply T, Audinot V, Boutin JA, Galizzi JP.; ''Cloning and molecular characterization of the novel human melanin-concentrating hormone receptor MCH2.''; PubMedEurope PMCScholia
Kato H, Matsumura Y, Maeda H.; ''Isolation and identification of hydroxyproline analogues of bradykinin in human urine.''; PubMedEurope PMCScholia
Knapp RJ, Malatynska E, Fang L, Li X, Babin E, Nguyen M, Santoro G, Varga EV, Hruby VJ, Roeske WR.; ''Identification of a human delta opioid receptor: cloning and expression.''; PubMedEurope PMCScholia
Homey B, Wang W, Soto H, Buchanan ME, Wiesenborn A, Catron D, Müller A, McClanahan TK, Dieu-Nosjean MC, Orozco R, Ruzicka T, Lehmann P, Oldham E, Zlotnik A.; ''Cutting edge: the orphan chemokine receptor G protein-coupled receptor-2 (GPR-2, CCR10) binds the skin-associated chemokine CCL27 (CTACK/ALP/ILC).''; PubMedEurope PMCScholia
Sausville E, Carney D, Battey J.; ''The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line.''; PubMedEurope PMCScholia
Noda M, Teranishi Y, Takahashi H, Toyosato M, Notake M, Nakanishi S, Numa S.; ''Isolation and structural organization of the human preproenkephalin gene.''; PubMedEurope PMCScholia
Tilly BC, Tertoolen LG, Lambrechts AC, Remorie R, de Laat SW, Moolenaar WH.; ''Histamine-H1-receptor-mediated phosphoinositide hydrolysis, Ca2+ signalling and membrane-potential oscillations in human HeLa carcinoma cells.''; PubMedEurope PMCScholia
Hinuma S, Habata Y, Fujii R, Kawamata Y, Hosoya M, Fukusumi S, Kitada C, Masuo Y, Asano T, Matsumoto H, Sekiguchi M, Kurokawa T, Nishimura O, Onda H, Fujino M.; ''A prolactin-releasing peptide in the brain.''; PubMedEurope PMCScholia
Gerard NP, Eddy RL, Shows TB, Gerard C.; ''The human neurokinin A (substance K) receptor. Molecular cloning of the gene, chromosome localization, and isolation of cDNA from tracheal and gastric tissues.''; PubMedEurope PMCScholia
Kinsella BT, O'Mahony DJ, Fitzgerald GA.; ''The human thromboxane A2 receptor alpha isoform (TP alpha) functionally couples to the G proteins Gq and G11 in vivo and is activated by the isoprostane 8-epi prostaglandin F2 alpha.''; PubMedEurope PMCScholia
De Backer MD, Gommeren W, Moereels H, Nobels G, Van Gompel P, Leysen JE, Luyten WH.; ''Genomic cloning, heterologous expression and pharmacological characterization of a human histamine H1 receptor.''; PubMedEurope PMCScholia
Communi D, Pirotton S, Parmentier M, Boeynaems JM.; ''Cloning and functional expression of a human uridine nucleotide receptor.''; PubMedEurope PMCScholia
Minth CD, Bloom SR, Polak JM, Dixon JE.; ''Cloning, characterization, and DNA sequence of a human cDNA encoding neuropeptide tyrosine.''; PubMedEurope PMCScholia
Lee JH, Bang E, Chae KJ, Kim JY, Lee DW, Lee W.; ''Solution structure of a new hypothalamic neuropeptide, human hypocretin-2/orexin-B.''; PubMedEurope PMCScholia
Gérard C, Mollereau C, Vassart G, Parmentier M.; ''Nucleotide sequence of a human cannabinoid receptor cDNA.''; PubMedEurope PMCScholia
Blondel O, Gastineau M, Dahmoune Y, Langlois M, Fischmeister R.; ''Cloning, expression, and pharmacology of four human 5-hydroxytryptamine 4 receptor isoforms produced by alternative splicing in the carboxyl terminus.''; PubMedEurope PMCScholia
Yokomizo T, Izumi T, Chang K, Takuwa Y, Shimizu T.; ''A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis.''; PubMedEurope PMCScholia
Hosoi T, Koguchi Y, Sugikawa E, Chikada A, Ogawa K, Tsuda N, Suto N, Tsunoda S, Taniguchi T, Ohnuki T.; ''Identification of a novel human eicosanoid receptor coupled to G(i/o).''; PubMedEurope PMCScholia
Vita N, Oury-Donat F, Chalon P, Guillemot M, Kaghad M, Bachy A, Thurneyssen O, Garcia S, Poinot-Chazel C, Casellas P, Keane P, Le Fur G, Maffrand JP, Soubrie P, Caput D, Ferrara P.; ''Neurotensin is an antagonist of the human neurotensin NT2 receptor expressed in Chinese hamster ovary cells.''; PubMedEurope PMCScholia
Worzfeld T, Wettschureck N, Offermanns S.; ''G(12)/G(13)-mediated signalling in mammalian physiology and disease.''; PubMedEurope PMCScholia
O'Dowd BF, Heiber M, Chan A, Heng HH, Tsui LC, Kennedy JL, Shi X, Petronis A, George SR, Nguyen T.; ''A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11.''; PubMedEurope PMCScholia
Peterfreund RA, MacCollin M, Gusella J, Fink JS.; ''Characterization and expression of the human A2a adenosine receptor gene.''; PubMedEurope PMCScholia
Communi D, Gonzalez NS, Detheux M, Brézillon S, Lannoy V, Parmentier M, Boeynaems JM.; ''Identification of a novel human ADP receptor coupled to G(i).''; PubMedEurope PMCScholia
Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K, Terao Y, Kumano S, Takatsu Y, Masuda Y, Ishibashi Y, Watanabe T, Asada M, Yamada T, Suenaga M, Kitada C, Usuki S, Kurokawa T, Onda H, Nishimura O, Fujino M.; ''Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.''; PubMedEurope PMCScholia
Boulay F, Tardif M, Brouchon L, Vignais P.; ''Synthesis and use of a novel N-formyl peptide derivative to isolate a human N-formyl peptide receptor cDNA.''; PubMedEurope PMCScholia
Bonini JA, Jones KA, Adham N, Forray C, Artymyshyn R, Durkin MM, Smith KE, Tamm JA, Boteju LW, Lakhlani PP, Raddatz R, Yao WJ, Ogozalek KL, Boyle N, Kouranova EV, Quan Y, Vaysse PJ, Wetzel JM, Branchek TA, Gerald C, Borowsky B.; ''Identification and characterization of two G protein-coupled receptors for neuropeptide FF.''; PubMedEurope PMCScholia
Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HH, Niznik HB.; ''Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1.''; PubMedEurope PMCScholia
Kubica J, Kozinski M, Navarese EP, Tantry U, Kubica A, Siller-Matula JM, Jeong YH, Fabiszak T, Andruszkiewicz A, Gurbel PA.; ''Cangrelor: an emerging therapeutic option for patients with coronary artery disease.''; PubMedEurope PMCScholia
Strauss U, Bräuer AU.; ''Current views on regulation and function of plasticity-related genes (PRGs/LPPRs) in the brain.''; PubMedEurope PMCScholia
Boel E, Schwartz TW, Norris KE, Fiil NP.; ''A cDNA encoding a small common precursor for human pancreatic polypeptide and pancreatic icosapeptide.''; PubMedEurope PMCScholia
Su SB, Gong W, Gao JL, Shen W, Murphy PM, Oppenheim JJ, Wang JM.; ''A seven-transmembrane, G protein-coupled receptor, FPRL1, mediates the chemotactic activity of serum amyloid A for human phagocytic cells.''; PubMedEurope PMCScholia
Nakamura T, Itadani H, Hidaka Y, Ohta M, Tanaka K.; ''Molecular cloning and characterization of a new human histamine receptor, HH4R.''; PubMedEurope PMCScholia
Nakabayashi K, Matsumi H, Bhalla A, Bae J, Mosselman S, Hsu SY, Hsueh AJ.; ''Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits, activates the thyroid-stimulating hormone receptor.''; PubMedEurope PMCScholia
Takeda Y, Chou KB, Takeda J, Sachais BS, Krause JE.; ''Molecular cloning, structural characterization and functional expression of the human substance P receptor.''; PubMedEurope PMCScholia
Im DS, Heise CE, Harding MA, George SR, O'Dowd BF, Theodorescu D, Lynch KR.; ''Molecular cloning and characterization of a lysophosphatidic acid receptor, Edg-7, expressed in prostate.''; PubMedEurope PMCScholia
Adrian K, Bernhard MK, Breitinger HG, Ogilvie A.; ''Expression of purinergic receptors (ionotropic P2X1-7 and metabotropic P2Y1-11) during myeloid differentiation of HL60 cells.''; PubMedEurope PMCScholia
Jacoby E, Bouhelal R, Gerspacher M, Seuwen K.; ''The 7 TM G-protein-coupled receptor target family.''; PubMedEurope PMCScholia
Boie Y, Rushmore TH, Darmon-Goodwin A, Grygorczyk R, Slipetz DM, Metters KM, Abramovitz M.; ''Cloning and expression of a cDNA for the human prostanoid IP receptor.''; PubMedEurope PMCScholia
Wang J, Simonavicius N, Wu X, Swaminath G, Reagan J, Tian H, Ling L.; ''Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35.''; PubMedEurope PMCScholia
Kobilka BK, Matsui H, Kobilka TS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ, Regan JW.; ''Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor.''; PubMedEurope PMCScholia
Ulrich CD, Ferber I, Holicky E, Hadac E, Buell G, Miller LJ.; ''Molecular cloning and functional expression of the human gallbladder cholecystokinin A receptor.''; PubMedEurope PMCScholia
Hoover DM, Boulegue C, Yang D, Oppenheim JJ, Tucker K, Lu W, Lubkowski J.; ''The structure of human macrophage inflammatory protein-3alpha /CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human beta-defensins.''; PubMedEurope PMCScholia
Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB.; ''Identification of the platelet ADP receptor targeted by antithrombotic drugs.''; PubMedEurope PMCScholia
Holmes WE, Lee J, Kuang WJ, Rice GC, Wood WI.; ''Structure and functional expression of a human interleukin-8 receptor.''; PubMedEurope PMCScholia
Vendelin J, Pulkkinen V, Rehn M, Pirskanen A, Räisänen-Sokolowski A, Laitinen A, Laitinen LA, Kere J, Laitinen T.; ''Characterization of GPRA, a novel G protein-coupled receptor related to asthma.''; PubMedEurope PMCScholia
Cain SA, Monk PN.; ''The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74).''; PubMedEurope PMCScholia
Bayewitch M, Avidor-Reiss T, Levy R, Barg J, Mechoulam R, Vogel Z.; ''The peripheral cannabinoid receptor: adenylate cyclase inhibition and G protein coupling.''; PubMedEurope PMCScholia
Langmead CJ, Szekeres PG, Chambers JK, Ratcliffe SJ, Jones DN, Hirst WD, Price GW, Herdon HJ.; ''Characterization of the binding of [(125)I]-human prolactin releasing peptide (PrRP) to GPR10, a novel G protein coupled receptor.''; PubMedEurope PMCScholia
Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O.; ''Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion.''; PubMedEurope PMCScholia
An S, Dickens MA, Bleu T, Hallmark OG, Goetzl EJ.; ''Molecular cloning of the human Edg2 protein and its identification as a functional cellular receptor for lysophosphatidic acid.''; PubMedEurope PMCScholia
Provencio I, Rodriguez IR, Jiang G, Hayes WP, Moreira EF, Rollag MD.; ''A novel human opsin in the inner retina.''; PubMedEurope PMCScholia
Harmar AJ, Armstrong A, Pascall JC, Chapman K, Rosie R, Curtis A, Going J, Edwards CR, Fink G.; ''cDNA sequence of human beta-preprotachykinin, the common precursor to substance P and neurokinin A.''; PubMedEurope PMCScholia
Ahmed K, Tunaru S, Langhans CD, Hanson J, Michalski CW, Kölker S, Jones PM, Okun JG, Offermanns S.; ''Deorphanization of GPR109B as a receptor for the beta-oxidation intermediate 3-OH-octanoic acid and its role in the regulation of lipolysis.''; PubMedEurope PMCScholia
Iida N, Grotendorst GR.; ''Cloning and sequencing of a new gro transcript from activated human monocytes: expression in leukocytes and wound tissue.''; PubMedEurope PMCScholia
Yamaguchi F, Tokuda M, Hatase O, Brenner S.; ''Molecular cloning of the novel human G protein-coupled receptor (GPCR) gene mapped on chromosome 9.''; PubMedEurope PMCScholia
Yu CR, Peden KW, Zaitseva MB, Golding H, Farber JM.; ''CCR9A and CCR9B: two receptors for the chemokine CCL25/TECK/Ck beta-15 that differ in their sensitivities to ligand.''; PubMedEurope PMCScholia
Zgombick JM, Schechter LE, Macchi M, Hartig PR, Branchek TA, Weinshank RL.; ''Human gene S31 encodes the pharmacologically defined serotonin 5-hydroxytryptamine1E receptor.''; PubMedEurope PMCScholia
Allgeier A, Offermanns S, Van Sande J, Spicher K, Schultz G, Dumont JE.; ''The human thyrotropin receptor activates G-proteins Gs and Gq/11.''; PubMedEurope PMCScholia
Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, Arenzana-Seisdedos F, Thelen M, Bachelerie F.; ''The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes.''; PubMedEurope PMCScholia
Kohno M, Hasegawa H, Inoue A, Muraoka M, Miyazaki T, Oka K, Yasukawa M.; ''Identification of N-arachidonylglycine as the endogenous ligand for orphan G-protein-coupled receptor GPR18.''; PubMedEurope PMCScholia
Briscoe CP, Tadayyon M, Andrews JL, Benson WG, Chambers JK, Eilert MM, Ellis C, Elshourbagy NA, Goetz AS, Minnick DT, Murdock PR, Sauls HR, Shabon U, Spinage LD, Strum JC, Szekeres PG, Tan KB, Way JM, Ignar DM, Wilson S, Muir AI.; ''The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids.''; PubMedEurope PMCScholia
Raddatz R, Wilson AE, Artymyshyn R, Bonini JA, Borowsky B, Boteju LW, Zhou S, Kouranova EV, Nagorny R, Guevarra MS, Dai M, Lerman GS, Vaysse PJ, Branchek TA, Gerald C, Forray C, Adham N.; ''Identification and characterization of two neuromedin U receptors differentially expressed in peripheral tissues and the central nervous system.''; PubMedEurope PMCScholia
Grandy DK, Marchionni MA, Makam H, Stofko RE, Alfano M, Frothingham L, Fischer JB, Burke-Howie KJ, Bunzow JR, Server AC.; ''Cloning of the cDNA and gene for a human D2 dopamine receptor.''; PubMedEurope PMCScholia
Schmuck K, Ullmer C, Engels P, Lübbert H.; ''Cloning and functional characterization of the human 5-HT2B serotonin receptor.''; PubMedEurope PMCScholia
Tobo M, Tomura H, Mogi C, Wang JQ, Liu JP, Komachi M, Damirin A, Kimura T, Murata N, Kurose H, Sato K, Okajima F.; ''Previously postulated "ligand-independent" signaling of GPR4 is mediated through proton-sensing mechanisms.''; PubMedEurope PMCScholia
Chambers JK, Macdonald LE, Sarau HM, Ames RS, Freeman K, Foley JJ, Zhu Y, McLaughlin MM, Murdock P, McMillan L, Trill J, Swift A, Aiyar N, Taylor P, Vawter L, Naheed S, Szekeres P, Hervieu G, Scott C, Watson JM, Murphy AJ, Duzic E, Klein C, Bergsma DJ, Wilson S, Livi GP.; ''A G protein-coupled receptor for UDP-glucose.''; PubMedEurope PMCScholia
Lee DK, Nguyen T, O'Neill GP, Cheng R, Liu Y, Howard AD, Coulombe N, Tan CP, Tang-Nguyen AT, George SR, O'Dowd BF.; ''Discovery of a receptor related to the galanin receptors.''; PubMedEurope PMCScholia
Soga T, Matsumoto Si, Oda T, Saito T, Hiyama H, Takasaki J, Kamohara M, Ohishi T, Matsushime H, Furuichi K.; ''Molecular cloning and characterization of prokineticin receptors.''; PubMedEurope PMCScholia
Hannun YA, Obeid LM.; ''Principles of bioactive lipid signalling: lessons from sphingolipids.''; PubMedEurope PMCScholia
Nathans J, Thomas D, Hogness DS.; ''Molecular genetics of human color vision: the genes encoding blue, green, and red pigments.''; PubMedEurope PMCScholia
Weinshank RL, Zgombick JM, Macchi MJ, Branchek TA, Hartig PR.; ''Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta.''; PubMedEurope PMCScholia
Vita N, Laurent P, Lefort S, Chalon P, Dumont X, Kaghad M, Gully D, Le Fur G, Ferrara P, Caput D.; ''Cloning and expression of a complementary DNA encoding a high affinity human neurotensin receptor.''; PubMedEurope PMCScholia
Boie Y, Sawyer N, Slipetz DM, Metters KM, Abramovitz M.; ''Molecular cloning and characterization of the human prostanoid DP receptor.''; PubMedEurope PMCScholia
O'Dowd BF, Scheideler MA, Nguyen T, Cheng R, Rasmussen JS, Marchese A, Zastawny R, Heng HH, Tsui LC, Shi X.; ''The cloning and chromosomal mapping of two novel human opioid-somatostatin-like receptor genes, GPR7 and GPR8, expressed in discrete areas of the brain.''; PubMedEurope PMCScholia
Sudo S, Kumagai J, Nishi S, Layfield S, Ferraro T, Bathgate RA, Hsueh AJ.; ''H3 relaxin is a specific ligand for LGR7 and activates the receptor by interacting with both the ectodomain and the exoloop 2.''; PubMedEurope PMCScholia
Ciana P, Fumagalli M, Trincavelli ML, Verderio C, Rosa P, Lecca D, Ferrario S, Parravicini C, Capra V, Gelosa P, Guerrini U, Belcredito S, Cimino M, Sironi L, Tremoli E, Rovati GE, Martini C, Abbracchio MP.; ''The orphan receptor GPR17 identified as a new dual uracil nucleotides/cysteinyl-leukotrienes receptor.''; PubMedEurope PMCScholia
Bodor ET, Waldo GL, Hooks SB, Corbitt J, Boyer JL, Harden TK.; ''Purification and functional reconstitution of the human P2Y12 receptor.''; PubMedEurope PMCScholia
An S, Bleu T, Zheng Y, Goetzl EJ.; ''Recombinant human G protein-coupled lysophosphatidic acid receptors mediate intracellular calcium mobilization.''; PubMedEurope PMCScholia
Kahn ML, Nakanishi-Matsui M, Shapiro MJ, Ishihara H, Coughlin SR.; ''Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin.''; PubMedEurope PMCScholia
Hess JF, Borkowski JA, Young GS, Strader CD, Ransom RW.; ''Cloning and pharmacological characterization of a human bradykinin (BK-2) receptor.''; PubMedEurope PMCScholia
Giros B, Martres MP, Sokoloff P, Schwartz JC.; ''[Gene cloning of human dopaminergic D3 receptor and identification of its chromosome]''; PubMedEurope PMCScholia
Sun H, Gilbert DJ, Copeland NG, Jenkins NA, Nathans J.; ''Peropsin, a novel visual pigment-like protein located in the apical microvilli of the retinal pigment epithelium.''; PubMedEurope PMCScholia
An S, Bleu T, Hallmark OG, Goetzl EJ.; ''Characterization of a novel subtype of human G protein-coupled receptor for lysophosphatidic acid.''; PubMedEurope PMCScholia
Wise A, Sheehan M, Rees S, Lee M, Milligan G.; ''Comparative analysis of the efficacy of A1 adenosine receptor activation of Gi/o alpha G proteins following coexpression of receptor and G protein and expression of A1 adenosine receptor-Gi/o alpha fusion proteins.''; PubMedEurope PMCScholia
Bräuner-Osborne H, Brann MR.; ''Pharmacology of muscarinic acetylcholine receptor subtypes (m1-m5): high throughput assays in mammalian cells.''; PubMedEurope PMCScholia
Reese EA, Bunzow JR, Arttamangkul S, Sonders MS, Grandy DK.; ''Trace amine-associated receptor 1 displays species-dependent stereoselectivity for isomers of methamphetamine, amphetamine, and para-hydroxyamphetamine.''; PubMedEurope PMCScholia
Bastien L, Sawyer N, Grygorczyk R, Metters KM, Adam M.; ''Cloning, functional expression, and characterization of the human prostaglandin E2 receptor EP2 subtype.''; PubMedEurope PMCScholia
Huang RR, Cheung AH, Mazina KE, Strader CD, Fong TM.; ''cDNA sequence and heterologous expression of the human neurokinin-3 receptor.''; PubMedEurope PMCScholia
Storjohann L, Holst B, Schwartz TW.; ''Molecular mechanism of Zn2+ agonism in the extracellular domain of GPR39.''; PubMedEurope PMCScholia
Dearry A, Gingrich JA, Falardeau P, Fremeau RT, Bates MD, Caron MG.; ''Molecular cloning and expression of the gene for a human D1 dopamine receptor.''; PubMedEurope PMCScholia
Winderickx J, Lindsey DT, Sanocki E, Teller DY, Motulsky AG, Deeb SS.; ''Polymorphism in red photopigment underlies variation in colour matching.''; PubMedEurope PMCScholia
Seeburg PH, Adelman JP.; ''Characterization of cDNA for precursor of human luteinizing hormone releasing hormone.''; PubMedEurope PMCScholia
Carrasco MP, Asbóth G, Phaneuf S, López Bernal A.; ''Activation of the prostaglandin FP receptor in human granulosa cells.''; PubMedEurope PMCScholia
Abramovitz M, Boie Y, Nguyen T, Rushmore TH, Bayne MA, Metters KM, Slipetz DM, Grygorczyk R.; ''Cloning and expression of a cDNA for the human prostanoid FP receptor.''; PubMedEurope PMCScholia
Wilson RJ, Rhodes SA, Wood RL, Shield VJ, Noel LS, Gray DW, Giles H.; ''Functional pharmacology of human prostanoid EP2 and EP4 receptors.''; PubMedEurope PMCScholia
Baker JG.; ''The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors.''; PubMedEurope PMCScholia
Perry SJ, Yi-Kung Huang E, Cronk D, Bagust J, Sharma R, Walker RJ, Wilson S, Burke JF.; ''A human gene encoding morphine modulating peptides related to NPFF and FMRFamide.''; PubMedEurope PMCScholia
Cernecka H, Sand C, Michel MC.; ''The odd sibling: features of β3-adrenoceptor pharmacology.''; PubMedEurope PMCScholia
Yamada Y, Post SR, Wang K, Tager HS, Bell GI, Seino S.; ''Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney.''; PubMedEurope PMCScholia
Corjay MH, Dobrzanski DJ, Way JM, Viallet J, Shapira H, Worland P, Sausville EA, Battey JF.; ''Two distinct bombesin receptor subtypes are expressed and functional in human lung carcinoma cells.''; PubMedEurope PMCScholia
Im DS, Heise CE, Ancellin N, O'Dowd BF, Shei GJ, Heavens RP, Rigby MR, Hla T, Mandala S, McAllister G, George SR, Lynch KR.; ''Characterization of a novel sphingosine 1-phosphate receptor, Edg-8.''; PubMedEurope PMCScholia
Cai TQ, Ren N, Jin L, Cheng K, Kash S, Chen R, Wright SD, Taggart AK, Waters MG.; ''Role of GPR81 in lactate-mediated reduction of adipose lipolysis.''; PubMedEurope PMCScholia
Smith KE, Walker MW, Artymyshyn R, Bard J, Borowsky B, Tamm JA, Yao WJ, Vaysse PJ, Branchek TA, Gerald C, Jones KA.; ''Cloned human and rat galanin GALR3 receptors. Pharmacology and activation of G-protein inwardly rectifying K+ channels.''; PubMedEurope PMCScholia
Power CA, Meyer A, Nemeth K, Bacon KB, Hoogewerf AJ, Proudfoot AE, Wells TN.; ''Molecular cloning and functional expression of a novel CC chemokine receptor cDNA from a human basophilic cell line.''; PubMedEurope PMCScholia
Chambers J, Ames RS, Bergsma D, Muir A, Fitzgerald LR, Hervieu G, Dytko GM, Foley JJ, Martin J, Liu WS, Park J, Ellis C, Ganguly S, Konchar S, Cluderay J, Leslie R, Wilson S, Sarau HM.; ''Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1.''; PubMedEurope PMCScholia
Adachi M, Yang YY, Furuichi Y, Miyamoto C.; ''Cloning and characterization of cDNA encoding human A-type endothelin receptor.''; PubMedEurope PMCScholia
Matsushima K, Morishita K, Yoshimura T, Lavu S, Kobayashi Y, Lew W, Appella E, Kung HF, Leonard EJ, Oppenheim JJ.; ''Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor.''; PubMedEurope PMCScholia
Yokomizo T, Kato K, Terawaki K, Izumi T, Shimizu T.; ''A second leukotriene B(4) receptor, BLT2. A new therapeutic target in inflammation and immunological disorders.''; PubMedEurope PMCScholia
Westman PC, Lipinski MJ, Torguson R, Waksman R.; ''A comparison of cangrelor, prasugrel, ticagrelor, and clopidogrel in patients undergoing percutaneous coronary intervention: A network meta-analysis.''; PubMedEurope PMCScholia
Yamagami S, Tokuda Y, Ishii K, Tanaka H, Endo N.; ''cDNA cloning and functional expression of a human monocyte chemoattractant protein 1 receptor.''; PubMedEurope PMCScholia
Habert-Ortoli E, Amiranoff B, Loquet I, Laburthe M, Mayaux JF.; ''Molecular cloning of a functional human galanin receptor.''; PubMedEurope PMCScholia
Gagnon AW, Manning DR, Catani L, Gewirtz A, Poncz M, Brass LF.; ''Identification of Gz alpha as a pertussis toxin-insensitive G protein in human platelets and megakaryocytes.''; PubMedEurope PMCScholia
Takahashi Y, Kato K, Hayashizaki Y, Wakabayashi T, Ohtsuka E, Matsuki S, Ikehara M, Matsubara K.; ''Molecular cloning of the human cholecystokinin gene by use of a synthetic probe containing deoxyinosine.''; PubMedEurope PMCScholia
Kolakowski LF, O'Neill GP, Howard AD, Broussard SR, Sullivan KA, Feighner SD, Sawzdargo M, Nguyen T, Kargman S, Shiao LL, Hreniuk DL, Tan CP, Evans J, Abramovitz M, Chateauneuf A, Coulombe N, Ng G, Johnson MP, Tharian A, Khoshbouei H, George SR, Smith RG, O'Dowd BF.; ''Molecular characterization and expression of cloned human galanin receptors GALR2 and GALR3.''; PubMedEurope PMCScholia
Hildebrandt JD.; ''Role of subunit diversity in signaling by heterotrimeric G proteins.''; PubMedEurope PMCScholia
Bazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, Greaves DR, Zlotnik A, Schall TJ.; ''A new class of membrane-bound chemokine with a CX3C motif.''; PubMedEurope PMCScholia
Mitsuhashi M, Mitsuhashi T, Payan DG.; ''Multiple signaling pathways of histamine H2 receptors. Identification of an H2 receptor-dependent Ca2+ mobilization pathway in human HL-60 promyelocytic leukemia cells.''; PubMedEurope PMCScholia
Hirasawa A, Tsumaya K, Awaji T, Katsuma S, Adachi T, Yamada M, Sugimoto Y, Miyazaki S, Tsujimoto G.; ''Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120.''; PubMedEurope PMCScholia
Zhang JY, Nawoschik S, Kowal D, Smith D, Spangler T, Ochalski R, Schechter L, Dunlop J.; ''Characterization of the 5-HT6 receptor coupled to Ca2+ signaling using an enabling chimeric G-protein.''; PubMedEurope PMCScholia
Salvatore CA, Jacobson MA, Taylor HE, Linden J, Johnson RG.; ''Molecular cloning and characterization of the human A3 adenosine receptor.''; PubMedEurope PMCScholia
Israili ZH.; ''Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension.''; PubMedEurope PMCScholia
Gilman AG.; ''G proteins: transducers of receptor-generated signals.''; PubMedEurope PMCScholia
Glaenzel U, Jin Y, Nufer R, Li W, Schroer K, Adam-Stitah S, Peter van Marle S, Legangneux E, Borell H, James AD, Meissner A, Camenisch G, Gardin A.; ''Metabolism and Disposition of Siponimod, a Novel Selective S1P1/S1P5 Agonist, in Healthy Volunteers and In Vitro Identification of Human Cytochrome P450 Enzymes Involved in Its Oxidative Metabolism.''; PubMedEurope PMCScholia
Lee DK, Nguyen T, Lynch KR, Cheng R, Vanti WB, Arkhitko O, Lewis T, Evans JF, George SR, O'Dowd BF.; ''Discovery and mapping of ten novel G protein-coupled receptor genes.''; PubMedEurope PMCScholia
Taggart AK, Kero J, Gan X, Cai TQ, Cheng K, Ippolito M, Ren N, Kaplan R, Wu K, Wu TJ, Jin L, Liaw C, Chen R, Richman J, Connolly D, Offermanns S, Wright SD, Waters MG.; ''(D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G.''; PubMedEurope PMCScholia
Pierce KD, Furlong TJ, Selbie LA, Shine J.; ''Molecular cloning and expression of an adenosine A2b receptor from human brain.''; PubMedEurope PMCScholia
Birnbaumer M, Seibold A, Gilbert S, Ishido M, Barberis C, Antaramian A, Brabet P, Rosenthal W.; ''Molecular cloning of the receptor for human antidiuretic hormone.''; PubMedEurope PMCScholia
ROCHA E SILVA M, BERALDO WT, ROSENFELD G.; ''Bradykinin, a hypotensive and smooth muscle stimulating factor released from plasma globulin by snake venoms and by trypsin.''; PubMedEurope PMCScholia
Xanthou G, Duchesnes CE, Williams TJ, Pease JE.; ''CCR3 functional responses are regulated by both CXCR3 and its ligands CXCL9, CXCL10 and CXCL11.''; PubMedEurope PMCScholia
Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C.; ''Trace amines: identification of a family of mammalian G protein-coupled receptors.''; PubMedEurope PMCScholia
Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, Meltzer HY, Sibley DR, Roth BL, Hamblin MW.; ''Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor.''; PubMedEurope PMCScholia
Stam NJ, Roesink C, Dijcks F, Garritsen A, van Herpen A, Olijve W.; ''Human serotonin 5-HT7 receptor: cloning and pharmacological characterisation of two receptor variants.''; PubMedEurope PMCScholia
Okuda-Ashitaka E, Minami T, Tachibana S, Yoshihara Y, Nishiuchi Y, Kimura T, Ito S.; ''Nocistatin, a peptide that blocks nociceptin action in pain transmission.''; PubMedEurope PMCScholia
Simonin F, Gavériaux-Ruff C, Befort K, Matthes H, Lannes B, Micheletti G, Mattéi MG, Charron G, Bloch B, Kieffer B.; ''kappa-Opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system.''; PubMedEurope PMCScholia
Lee CW, Rivera R, Dubin AE, Chun J.; ''LPA(4)/GPR23 is a lysophosphatidic acid (LPA) receptor utilizing G(s)-, G(q)/G(i)-mediated calcium signaling and G(12/13)-mediated Rho activation.''; PubMedEurope PMCScholia
Mountjoy KG, Robbins LS, Mortrud MT, Cone RD.; ''The cloning of a family of genes that encode the melanocortin receptors.''; PubMedEurope PMCScholia
Lüttichau HR, Clark-Lewis I, Jensen PØ, Moser C, Gerstoft J, Schwartz TW.; ''A highly selective CCR2 chemokine agonist encoded by human herpesvirus 6.''; PubMedEurope PMCScholia
Sugimoto T, Saito M, Mochizuki S, Watanabe Y, Hashimoto S, Kawashima H.; ''Molecular cloning and functional expression of a cDNA encoding the human V1b vasopressin receptor.''; PubMedEurope PMCScholia
Richmond A, Balentien E, Thomas HG, Flaggs G, Barton DE, Spiess J, Bordoni R, Francke U, Derynck R.; ''Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to beta-thromboglobulin.''; PubMedEurope PMCScholia
An S, Zheng Y, Bleu T.; ''Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5.''; PubMedEurope PMCScholia
Ludwig MG, Vanek M, Guerini D, Gasser JA, Jones CE, Junker U, Hofstetter H, Wolf RM, Seuwen K.; ''Proton-sensing G-protein-coupled receptors.''; PubMedEurope PMCScholia
Comb M, Seeburg PH, Adelman J, Eiden L, Herbert E.; ''Primary structure of the human Met- and Leu-enkephalin precursor and its mRNA.''; PubMedEurope PMCScholia
Saltiel E, Ward A.; ''Ticlopidine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in platelet-dependent disease states.''; PubMedEurope PMCScholia
Pan S, Gray NS, Gao W, Mi Y, Fan Y, Wang X, Tuntland T, Che J, Lefebvre S, Chen Y, Chu A, Hinterding K, Gardin A, End P, Heining P, Bruns C, Cooke NG, Nuesslein-Hildesheim B.; ''Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator.''; PubMedEurope PMCScholia
Yoshida T, Imai T, Kakizaki M, Nishimura M, Yoshie O.; ''Molecular cloning of a novel C or gamma type chemokine, SCM-1.''; PubMedEurope PMCScholia
Chun J, Hartung HP.; ''Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis.''; PubMedEurope PMCScholia
Van Tol HH, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, Civelli O.; ''Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine.''; PubMedEurope PMCScholia
Haskill S, Peace A, Morris J, Sporn SA, Anisowicz A, Lee SW, Smith T, Martin G, Ralph P, Sager R.; ''Identification of three related human GRO genes encoding cytokine functions.''; PubMedEurope PMCScholia
Parker EM, Xia L.; ''Extensive alternative splicing in the 5'-untranslated region of the rat and human neuropeptide Y Y5 receptor genes regulates receptor expression.''; PubMedEurope PMCScholia
Tiffany HL, Lautens LL, Gao JL, Pease J, Locati M, Combadiere C, Modi W, Bonner TI, Murphy PM.; ''Identification of CCR8: a human monocyte and thymus receptor for the CC chemokine I-309.''; PubMedEurope PMCScholia
Feldman DS, Zamah AM, Pierce KL, Miller WE, Kelly F, Rapacciuolo A, Rockman HA, Koch WJ, Luttrell LM.; ''Selective inhibition of heterotrimeric Gs signaling. Targeting the receptor-G protein interface using a peptide minigene encoding the Galpha(s) carboxyl terminus.''; PubMedEurope PMCScholia
Qi AD, Kennedy C, Harden TK, Nicholas RA.; ''Differential coupling of the human P2Y(11) receptor to phospholipase C and adenylyl cyclase.''; PubMedEurope PMCScholia
Jarmin DI, Rits M, Bota D, Gerard NP, Graham GJ, Clark-Lewis I, Gerard C.; ''Cutting edge: identification of the orphan receptor G-protein-coupled receptor 2 as CCR10, a specific receptor for the chemokine ESkine.''; PubMedEurope PMCScholia
Kursar JD, Nelson DL, Wainscott DB, Baez M.; ''Molecular cloning, functional expression, and mRNA tissue distribution of the human 5-hydroxytryptamine2B receptor.''; PubMedEurope PMCScholia
Noble S, Goa KL.; ''Ticlopidine. A review of its pharmacology, clinical efficacy and tolerability in the prevention of cerebral ischaemia and stroke.''; PubMedEurope PMCScholia
Saito S, Matsui H, Kawano M, Kumagai K, Tomishige N, Hanada K, Echigo S, Tamura S, Kobayashi T.; ''Protein phosphatase 2Cepsilon is an endoplasmic reticulum integral membrane protein that dephosphorylates the ceramide transport protein CERT to enhance its association with organelle membranes.''; PubMedEurope PMCScholia
Léon C, Vial C, Cazenave JP, Gachet C.; ''Cloning and sequencing of a human cDNA encoding endothelial P2Y1 purinoceptor.''; PubMedEurope PMCScholia
Jones CE, Holden S, Tenaillon L, Bhatia U, Seuwen K, Tranter P, Turner J, Kettle R, Bouhelal R, Charlton S, Nirmala NR, Jarai G, Finan P.; ''Expression and characterization of a 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid receptor highly expressed on human eosinophils and neutrophils.''; PubMedEurope PMCScholia
Lin SL, Setya S, Johnson-Farley NN, Cowen DS.; ''Differential coupling of 5-HT(1) receptors to G proteins of the G(i) family.''; PubMedEurope PMCScholia
Van den Wyngaert I, Gommeren W, Verhasselt P, Jurzak M, Leysen J, Luyten W, Bender E.; ''Cloning and expression of a human serotonin 5-HT4 receptor cDNA.''; PubMedEurope PMCScholia
Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF.; ''Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor.''; PubMedEurope PMCScholia
Jiang Y, Luo L, Gustafson EL, Yadav D, Laverty M, Murgolo N, Vassileva G, Zeng M, Laz TM, Behan J, Qiu P, Wang L, Wang S, Bayne M, Greene J, Monsma F, Zhang FL.; ''Identification and characterization of a novel RF-amide peptide ligand for orphan G-protein-coupled receptor SP9155.''; PubMedEurope PMCScholia
Rosenkilde MM, Benned-Jensen T, Andersen H, Holst PJ, Kledal TN, Lüttichau HR, Larsen JK, Christensen JP, Schwartz TW.; ''Molecular pharmacological phenotyping of EBI2. An orphan seven-transmembrane receptor with constitutive activity.''; PubMedEurope PMCScholia
Thomas P, Pang Y, Filardo EJ, Dong J.; ''Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells.''; PubMedEurope PMCScholia
Williams JR, Khandoga AL, Goyal P, Fells JI, Perygin DH, Siess W, Parrill AL, Tigyi G, Fujiwara Y.; ''Unique ligand selectivity of the GPR92/LPA5 lysophosphatidate receptor indicates role in human platelet activation.''; PubMedEurope PMCScholia
Le Y, Gong W, Tiffany HL, Tumanov A, Nedospasov S, Shen W, Dunlop NM, Gao JL, Murphy PM, Oppenheim JJ, Wang JM.; ''Amyloid (beta)42 activates a G-protein-coupled chemoattractant receptor, FPR-like-1.''; PubMedEurope PMCScholia
Weitz CJ, Miyake Y, Shinzato K, Montag E, Zrenner E, Went LN, Nathans J.; ''Human tritanopia associated with two amino acid substitutions in the blue-sensitive opsin.''; PubMedEurope PMCScholia
Zaballos A, Gutiérrez J, Varona R, Ardavín C, Márquez G.; ''Cutting edge: identification of the orphan chemokine receptor GPR-9-6 as CCR9, the receptor for the chemokine TECK.''; PubMedEurope PMCScholia
Tournamille C, Filipe A, Wasniowska K, Gane P, Lisowska E, Cartron JP, Colin Y, Le Van Kim C.; ''Structure-function analysis of the extracellular domains of the Duffy antigen/receptor for chemokines: characterization of antibody and chemokine binding sites.''; PubMedEurope PMCScholia
Fathi Z, Battaglino PM, Iben LG, Li H, Baker E, Zhang D, McGovern R, Mahle CD, Sutherland GR, Iismaa TP, Dickinson KE, Zimanyi IA.; ''Molecular characterization, pharmacological properties and chromosomal localization of the human GALR2 galanin receptor.''; PubMedEurope PMCScholia
Liu C, Eriste E, Sutton S, Chen J, Roland B, Kuei C, Farmer N, Jörnvall H, Sillard R, Lovenberg TW.; ''Identification of relaxin-3/INSL7 as an endogenous ligand for the orphan G-protein-coupled receptor GPCR135.''; PubMedEurope PMCScholia
Capra V, Bolla M, Belloni PA, Mezzetti M, Folco GC, Nicosia S, Rovati GE.; ''Pharmacological characterization of the cysteinyl-leukotriene antagonists CGP 45715A (iralukast) and CGP 57698 in human airways in vitro.''; PubMedEurope PMCScholia
Pereillo JM, Maftouh M, Andrieu A, Uzabiaga MF, Fedeli O, Savi P, Pascal M, Herbert JM, Maffrand JP, Picard C.; ''Structure and stereochemistry of the active metabolite of clopidogrel.''; PubMedEurope PMCScholia
White RB, Eisen JA, Kasten TL, Fernald RD.; ''Second gene for gonadotropin-releasing hormone in humans.''; PubMedEurope PMCScholia
Uguccioni M, Mackay CR, Ochensberger B, Loetscher P, Rhis S, LaRosa GJ, Rao P, Ponath PD, Baggiolini M, Dahinden CA.; ''High expression of the chemokine receptor CCR3 in human blood basophils. Role in activation by eotaxin, MCP-4, and other chemokines.''; PubMedEurope PMCScholia
Armstrong RA, Lawrence RA, Jones RL, Wilson NH, Collier A.; ''Functional and ligand binding studies suggest heterogeneity of platelet prostacyclin receptors.''; PubMedEurope PMCScholia
Checler F, Vincent JP, Kitabgi P.; ''Purification and characterization of a novel neurotensin-degrading peptidase from rat brain synaptic membranes.''; PubMedEurope PMCScholia
Adham N, Kao HT, Schecter LE, Bard J, Olsen M, Urquhart D, Durkin M, Hartig PR, Weinshank RL, Branchek TA.; ''Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase.''; PubMedEurope PMCScholia
Murphy PM, Tiffany HL.; ''Cloning of complementary DNA encoding a functional human interleukin-8 receptor.''; PubMedEurope PMCScholia
Kawamata Y, Fujii R, Hosoya M, Harada M, Yoshida H, Miwa M, Fukusumi S, Habata Y, Itoh T, Shintani Y, Hinuma S, Fujisawa Y, Fujino M.; ''A G protein-coupled receptor responsive to bile acids.''; PubMedEurope PMCScholia
Aungraheeta R, Conibear A, Butler M, Kelly E, Nylander S, Mumford A, Mundell SJ.; ''Inverse agonism at the P2Y12 receptor and ENT1 transporter blockade contribute to platelet inhibition by ticagrelor.''; PubMedEurope PMCScholia
Lynch KR, O'Neill GP, Liu Q, Im DS, Sawyer N, Metters KM, Coulombe N, Abramovitz M, Figueroa DJ, Zeng Z, Connolly BM, Bai C, Austin CP, Chateauneuf A, Stocco R, Greig GM, Kargman S, Hooks SB, Hosfield E, Williams DL, Ford-Hutchinson AW, Caskey CT, Evans JF.; ''Characterization of the human cysteinyl leukotriene CysLT1 receptor.''; PubMedEurope PMCScholia
Stitham J, Stojanovic A, Merenick BL, O'Hara KA, Hwa J.; ''The unique ligand-binding pocket for the human prostacyclin receptor. Site-directed mutagenesis and molecular modeling.''; PubMedEurope PMCScholia
Gerald C, Walker MW, Vaysse PJ, He C, Branchek TA, Weinshank RL.; ''Expression cloning and pharmacological characterization of a human hippocampal neuropeptide Y/peptide YY Y2 receptor subtype.''; PubMedEurope PMCScholia
Jia XC, Oikawa M, Bo M, Tanaka T, Ny T, Boime I, Hsueh AJ.; ''Expression of human luteinizing hormone (LH) receptor: interaction with LH and chorionic gonadotropin from human but not equine, rat, and ovine species.''; PubMedEurope PMCScholia
Arita M, Ohira T, Sun YP, Elangovan S, Chiang N, Serhan CN.; ''Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation.''; PubMedEurope PMCScholia
Stam NJ, Van Huizen F, Van Alebeek C, Brands J, Dijkema R, Tonnaer JA, Olijve W.; ''Genomic organization, coding sequence and functional expression of human 5-HT2 and 5-HT1A receptor genes.''; PubMedEurope PMCScholia
Wise A, Foord SM, Fraser NJ, Barnes AA, Elshourbagy N, Eilert M, Ignar DM, Murdock PR, Steplewski K, Green A, Brown AJ, Dowell SJ, Szekeres PG, Hassall DG, Marshall FH, Wilson S, Pike NB.; ''Molecular identification of high and low affinity receptors for nicotinic acid.''; PubMedEurope PMCScholia
Wenzel-Seifert K, Liu HY, Seifert R.; ''Similarities and differences in the coupling of human beta1- and beta2-adrenoceptors to Gs(alpha) splice variants.''; PubMedEurope PMCScholia
Sarau HM, Ames RS, Chambers J, Ellis C, Elshourbagy N, Foley JJ, Schmidt DB, Muccitelli RM, Jenkins O, Murdock PR, Herrity NC, Halsey W, Sathe G, Muir AI, Nuthulaganti P, Dytko GM, Buckley PT, Wilson S, Bergsma DJ, Hay DW.; ''Identification, molecular cloning, expression, and characterization of a cysteinyl leukotriene receptor.''; PubMedEurope PMCScholia
Bandoh K, Aoki J, Hosono H, Kobayashi S, Kobayashi T, Murakami-Murofushi K, Tsujimoto M, Arai H, Inoue K.; ''Molecular cloning and characterization of a novel human G-protein-coupled receptor, EDG7, for lysophosphatidic acid.''; PubMedEurope PMCScholia
Ye RD, Prossnitz ER, Zou AH, Cochrane CG.; ''Characterization of a human cDNA that encodes a functional receptor for platelet activating factor.''; PubMedEurope PMCScholia
Munro S, Thomas KL, Abu-Shaar M.; ''Molecular characterization of a peripheral receptor for cannabinoids.''; PubMedEurope PMCScholia
Ye RD, Cavanagh SL, Quehenberger O, Prossnitz ER, Cochrane CG.; ''Isolation of a cDNA that encodes a novel granulocyte N-formyl peptide receptor.''; PubMedEurope PMCScholia
Legler DF, Loetscher M, Roos RS, Clark-Lewis I, Baggiolini M, Moser B.; ''B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5.''; PubMedEurope PMCScholia
Birkenbach M, Josefsen K, Yalamanchili R, Lenoir G, Kieff E.; ''Epstein-Barr virus-induced genes: first lymphocyte-specific G protein-coupled peptide receptors.''; PubMedEurope PMCScholia
Elshourbagy NA, Korman DR, Wu HL, Sylvester DR, Lee JA, Nuthalaganti P, Bergsma DJ, Kumar CS, Nambi P.; ''Molecular characterization and regulation of the human endothelin receptors.''; PubMedEurope PMCScholia
Kothapalli R, Kusmartseva I, Loughran TP.; ''Characterization of a human sphingosine-1-phosphate receptor gene (S1P5) and its differential expression in LGL leukemia.''; PubMedEurope PMCScholia
Bhadada SV, Patel BM, Mehta AA, Goyal RK.; ''β(3) Receptors: Role in Cardiometabolic Disorders.''; PubMedEurope PMCScholia
Gantz I, Munzert G, Tashiro T, Schäffer M, Wang L, DelValle J, Yamada T.; ''Molecular cloning of the human histamine H2 receptor.''; PubMedEurope PMCScholia
Ames RS, Li Y, Sarau HM, Nuthulaganti P, Foley JJ, Ellis C, Zeng Z, Su K, Jurewicz AJ, Hertzberg RP, Bergsma DJ, Kumar C.; ''Molecular cloning and characterization of the human anaphylatoxin C3a receptor.''; PubMedEurope PMCScholia
Regan JW, Bailey TJ, Pepperl DJ, Pierce KL, Bogardus AM, Donello JE, Fairbairn CE, Kedzie KM, Woodward DF, Gil DW.; ''Cloning of a novel human prostaglandin receptor with characteristics of the pharmacologically defined EP2 subtype.''; PubMedEurope PMCScholia
Lee CW, Rivera R, Gardell S, Dubin AE, Chun J.; ''GPR92 as a new G12/13- and Gq-coupled lysophosphatidic acid receptor that increases cAMP, LPA5.''; PubMedEurope PMCScholia
Bergsma DJ, Ellis C, Kumar C, Nuthulaganti P, Kersten H, Elshourbagy N, Griffin E, Stadel JM, Aiyar N.; ''Cloning and characterization of a human angiotensin II type 1 receptor.''; PubMedEurope PMCScholia
Lee S, Lin M, Mele A, Cao Y, Farmar J, Russo D, Redman C.; ''Proteolytic processing of big endothelin-3 by the kell blood group protein.''; PubMedEurope PMCScholia
Mohr E, Hillers M, Ivell R, Haulica ID, Richter D.; ''Expression of the vasopressin and oxytocin genes in human hypothalami.''; PubMedEurope PMCScholia
Liu C, Chen J, Sutton S, Roland B, Kuei C, Farmer N, Sillard R, Lovenberg TW.; ''Identification of relaxin-3/INSL7 as a ligand for GPCR142.''; PubMedEurope PMCScholia
Schmid A, Thierauch KH, Schleuning WD, Dinter H.; ''Splice variants of the human EP3 receptor for prostaglandin E2.''; PubMedEurope PMCScholia
Van Brocklyn JR, Gräler MH, Bernhardt G, Hobson JP, Lipp M, Spiegel S.; ''Sphingosine-1-phosphate is a ligand for the G protein-coupled receptor EDG-6.''; PubMedEurope PMCScholia
Morimura H, Saindelle-Ribeaudeau F, Berson EL, Dryja TP.; ''Mutations in RGR, encoding a light-sensitive opsin homologue, in patients with retinitis pigmentosa.''; PubMedEurope PMCScholia
Seiler S, Brassard CL, Federici ME.; ''SQ-27986 inhibition of platelet aggregation is mediated through activation of platelet prostaglandin D2 receptors.''; PubMedEurope PMCScholia
Russo D, Redman C, Lee S.; ''Association of XK and Kell blood group proteins.''; PubMedEurope PMCScholia
Sugo T, Murakami Y, Shimomura Y, Harada M, Abe M, Ishibashi Y, Kitada C, Miyajima N, Suzuki N, Mori M, Fujino M.; ''Identification of urotensin II-related peptide as the urotensin II-immunoreactive molecule in the rat brain.''; PubMedEurope PMCScholia
Hla T, Maciag T.; ''An abundant transcript induced in differentiating human endothelial cells encodes a polypeptide with structural similarities to G-protein-coupled receptors.''; PubMedEurope PMCScholia
Peralta EG, Ashkenazi A, Winslow JW, Smith DH, Ramachandran J, Capon DJ.; ''Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors.''; PubMedEurope PMCScholia
Lopez VM, Decatur CL, Stamer WD, Lynch RM, McKay BS.; ''L-DOPA is an endogenous ligand for OA1.''; PubMedEurope PMCScholia
Faurholm B, Millar RP, Katz AA.; ''The genes encoding the type II gonadotropin-releasing hormone receptor and the ribonucleoprotein RBM8A in humans overlap in two genomic loci.''; PubMedEurope PMCScholia
Liao F, Alkhatib G, Peden KW, Sharma G, Berger EA, Farber JM.; ''STRL33, A novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1.''; PubMedEurope PMCScholia
Minegishi T, Nakamura K, Takakura Y, Miyamoto K, Hasegawa Y, Ibuki Y, Igarashi M, Minegish T [corrected to Minegishi T].; ''Cloning and sequencing of human LH/hCG receptor cDNA.''; PubMedEurope PMCScholia
Nagayama Y, Kaufman KD, Seto P, Rapoport B.; ''Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor.''; PubMedEurope PMCScholia
Bonner TI, Young AC, Brann MR, Buckley NJ.; ''Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes.''; PubMedEurope PMCScholia
Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE.; ''The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells.''; PubMedEurope PMCScholia
Blackshaw S, Snyder SH.; ''Encephalopsin: a novel mammalian extraretinal opsin discretely localized in the brain.''; PubMedEurope PMCScholia
Minegishi T, Nakamura K, Takakura Y, Ibuki Y, Igarashi M, Minegish T [corrected to Minegishi T].; ''Cloning and sequencing of human FSH receptor cDNA.''; PubMedEurope PMCScholia
Ding Z, Kim S, Dorsam RT, Jin J, Kunapuli SP.; ''Inactivation of the human P2Y12 receptor by thiol reagents requires interaction with both extracellular cysteine residues, Cys17 and Cys270.''; PubMedEurope PMCScholia
VAN Giezen JJ, Nilsson L, Berntsson P, Wissing BM, Giordanetto F, Tomlinson W, Greasley PJ.; ''Ticagrelor binds to human P2Y(12) independently from ADP but antagonizes ADP-induced receptor signaling and platelet aggregation.''; PubMedEurope PMCScholia
Chemokine-like receptor 1 (CMKLR1, ERV1, CHEMR23, DEZ) is activated by the essentil fatty acid-derived, pro-inflammation resolving ligand resolvin E1 (RvE1), which is the result of sequential enzymatic conversion of the omega-3 fatty acid eicosapentaenoic acid (EPA) by aspirin-modified cyclooxygenase or cytochrome P450 and 5-lipoxygenase. RvE1 is produced in both 18(S)- and 18(R)-stereoisomeric forms (Arita et al. 2005, 2007).
CMKLR1 is also reported to be a receptor for chemerin (Wittamer et al. 2003) and RvE1 is reported to be a partial agonist for Leukotriene B4 receptor 1 (LTB4R, BLT1, CMKRL1) (Arita et al. 2007).
CMKLR1 signals via the Akt/rS6/mTOR pathway (Ohira et al. 2010). This RvE1 mediated signaling influences is believed to actively promote the resolution of inflammation (Freire et al. 2017).
Chemokine-like receptor 1 (CMKLR1, ERV1, CHEMR23, DEZ) is activated by the essentil fatty acid-derived, pro-inflammation resolving ligand resolvin E1 (RvE1), which is the result of sequential enzymatic conversion of the omega-3 fatty acid eicosapentaenoic acid (EPA) by aspirin-modified cyclooxygenase or cytochrome P450 and 5-lipoxygenase. RvE1 is produced in both 18(S)- and 18(R)-stereoisomeric forms (Arita et al. 2005, 2007).
CMKLR1 is also reported to be a receptor for chemerin (Wittamer et al. 2003) and RvE1 is reported to be a partial agonist for Leukotriene B4 receptor 1 (LTB4R, BLT1, CMKRL1) (Arita et al. 2007).
CMKLR1 signals via the Akt/rS6/mTOR pathway (Ohira et al. 2010). This RvE1 mediated signaling influences is believed to actively promote the resolution of inflammation (Freire et al. 2017).
This is the inactive form of the receptor, before protease activation. Proteinase (protease) activated receptors are activated by the cleavage of an N-terminal extracellular segment by serine proteases, particularly thrombin which activates PAR1, 3 and 4. The cleaved fragment is an activating ligand for the receptor; synthetic peptide mimics of the N-terminal fragment can activate uncleaved receptors.
This is the inactive form of the receptor, before protease activation. Proteinase (protease) activated receptors are activated by the cleavage of an N-terminal extracellular segment by serine proteases, particularly thrombin which activates PAR1, 3 and 4. The cleaved fragment is an activating ligand for the receptor; synthetic peptide mimics of the N-terminal fragment can activate uncleaved receptors.
This is the inactive form of the receptor, before protease activation. Proteinase (protease) activated receptors are activated by the cleavage of an N-terminal extracellular segment by serine proteases, particularly thrombin which activates PAR1, 3 and 4. The cleaved fragment is an activating ligand for the receptor; synthetic peptide mimics of the N-terminal fragment can activate uncleaved receptors.
This is the inactive form of the receptor, before protease activation. Proteinase (protease) activated receptors are activated by the cleavage of an N-terminal extracellular segment by serine proteases, particularly thrombin which activates PAR1, 3 and 4. The cleaved fragment is an activating ligand for the receptor; synthetic peptide mimics of the N-terminal fragment can activate uncleaved receptors.
The Free fatty acid receptor 1 (FFAR1 or GPR40) is located on pancreatic beta cells and binds to medium and long chain fatty acids (fatty acids having more than 12 carbon groups). FFAR1 is a G-protein coupled receptor that is coupled to Gq.
The G12/13 family is probably the least well characterized subtype, partly because G12/13 coupling is difficult to determine when compared with the other subtypes which predominantly rely on assay technologies that measure intracellular calcium. The G12/13 family are best known for their involvement in the processes of cell proliferation and morphology, such as stress fiber and focal adhesion formation. Interactions with Rho guanine nucleotide exchange factors (RhoGEFs) are thought to mediate many of these processes. (Buhl et al.1995, Sugimoto et al. 2003). Activation of Rho or the regulation of events through Rho is often taken as evidence of G12/13 signaling. Receptors that are coupled with G12/13 invariably couple with one or more other G protein subtypes, usually Gq.
The classical signalling mechanism for G alpha (i) is inhibition of the cAMP dependent pathway through inhibition of adenylate cyclase (Dessauer C W et al. 2002). Decreased production of cAMP from ATP results in decreased activity of cAMP-dependent protein kinases. Other functions of G alpha (i) includes activation of the protein tyrosine kinase c-Src (Ma Y C et al. 2000). Regulator of G-protein Signalling (RGS) proteins can regulate the activity of G alpha (i) (Soundararajan et al. 2008).
The classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides a path to calcium-regulated kinases and phosphatases, GEFs, MAP kinase cassettes and other proteins that mediate cellular responses ranging from granule secretion, integrin activation, and aggregation in platelets. Gq participates in many other signalling events including direct interaction with RhoGEFs that stimulate RhoA activity and inhibition of PI3K. Both in vitro and in vivo, the G-protein Gq seems to be the predominant mediator of the activation of platelets. Moreover, G alpha (q) can stimulate the activation of Burton tyrosine kinase (Ma Y C et al. 1998). Regulator of G-protein Signalling (RGS) proteins can regulate the activity of G alpha (z) (Soundararajan M et al. 2008).
The general function of the G alpha (s) subunit (Gs) is to activate adenylate cyclase (Tesmer et al. 1997), which in turn produces cAMP, leading to the activation of cAMP-dependent protein kinases (often referred to collectively as Protein Kinase A). The signal from the ligand-stimulated GPCR is amplified because the receptor can activate several Gs heterotrimers before it is inactivated. Another downstream effector of G alpha (s) is the protein tyrosine kinase c-Src (Ma et al. 2000).
The heterotrimeric G protein G alpha (z), is a member of the G (i) family. Unlike other G alpha (i) family members it lacks an ADP ribosylation site cysteine four residues from the carboxyl terminus and is thus pertussis toxin-insensitive. It inhibits adenylyl cyclase types I, V and VI (Wong Y H et al. 1992). G alpha (z) interacts with the Rap1 GTPase activating protein (Rap1GAP) to attenuate Rap1 signaling. Like all G-proteins G alpha (z) has an intrinsic GTPase activity, but this activity tends to be lower for the pertussis toxin insensitive G-proteins, most strikingly so for G alpha (z), whose kcat value for GTP hydrolysis is 200-fold lower than those of G alpha (s) or G alpha (i) (Grazziano et al. 1989). G alpha (z) knockout mice have disrupted platelet aggregation at physiological concentrations of epinephrine and responses to several neuroactive drugs are altered (Yang et al. 2000). Regulator of G-protein Signalling (RGS) proteins can regulate the activity of G alpha (z) (Soundararajan M et al. 2008).
GPR183 (originally called EBI2) binds the oxysterol 7alpha,25-dihydroxycholesterol (7a,25-OHC) (Hannedouche et al. 2011, Liu et al. 2011). GPR183 is believed to played a key role in regulating B cell migration and responses (Gatto et al. 2009, Pereira et al. 2009, Yi et al. 2012, Sun & Liu 2015). It signals via Gi (Rosenkilde et al. 2006).
GPR183 (originally called EBI2) binds the oxysterol 7alpha,25-dihydroxycholesterol (7a,25-OHC) (Hannedouche et al. 2011, Liu et al. 2011). GPR183 is believed to played a key role in regulating B cell migration and responses (Gatto et al. 2009, Pereira et al. 2009, Yi et al. 2012, Sun & Liu 2015). It signals via Gi (Rosenkilde et al. 2006).
Paper describes 'full-length' prosaposin but methods indicate a 'C-teminal fragment' so the actual fragment represented by this full-length prosaposin is unclear.
SUCNR1 (GPR91) is activated by the citric acid cycle intermediate succinate (SUCCA) (He et al. 2004), signalling via Gi to have a role in the stimulation of hematopoietic progenitor cell (HPC) growth (Hakak et al. 2009).
CCRL2 binds the chemokine CCL19 with an affinity similar to the binding of CCL19 to its other receptor CCR7. In contrast to the known CCL19:CCR7 ligand:receptor interaction, binding to CCRL2 does not result in cellular activation. Instead CCRL2 is constitutively recycled via clathrin-coated pits. Thus CCRL2 may have a role in modulating chemokine-triggered immune responses by capturing and internalizing CCL19.
GPR31 binds with high affinity the 12-lipoxygenase-derived product 12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE). 12-(S)-HETE/GPR31-mediated ERK1/2 activation was inhibited by pertussis toxin, suggesting that the involvement of the G-alpha-i/o heterotrimeric G proteins.
HCAR3 (GPR109B) is activated by 3-hydroxyoctanoic acid (3HO) (Ahmed et al. 2009) and nicotinic acid (niacin) (Wise et al. 2003). 3HO is an intermediate of fatty acid beta-oxidation. Under conditions of increased beta-oxidation flux, such as during starvation, under a ketogenic diet, or in patients with diabetic ketoacidosis, 3HO plasma concentrations are sufficient to activate the HCAR3 receptor (Costa et al. 1998, Jones et al. 2002, Ahmed et al. 2009).
Three receptors have a common CC chemokine CCL5 that can signal through them. CCR3 (Combadiere C et al, 1995) is highly expressed in eosinophils and basophils and also found in airway epithelial cells, thus implicating this receptor in allergic reactions. CCR4 (Power CA et al, 1995) is expressed in Th2 T lymphocytes and upregulated by T-cell receptor activation. CCR5 (Samson M et al, 1996) mediates the recruitment of cells involved in immune and inflammatory processes.
CCR7 (Epstein-Barr virus-induced gene 1, EBI1) (Birkenbach M, 1993; Schweickart VL et al, 1994) plays an important role in the trafficking of B and T lymphocytes and dendritic cells across high endothelial venules. Both CCL19 (Macrophage inflammatory protein 3 beta, MIP-3-beta; EBI1-ligand chemokine, ELC) (Yoshida R et al, 1997) and CCL21 (Secondary lymphoid-tissue chemokine, SLC; Beta chemokine exodus-2) (Yoshida R et al, 1998) bind specifically to CCR7.
These three receptors can all bind the CC chemokine CCL16. CCR1 was the first CC chemokine receptor identified (Neote K et al, 1993) and can bind multiple chemokines. CCR1 is found on blood lymphocytes and monocytes. CCR2 is found on monocytes, B cells, activated memory T cells and basophils (Yamagami S et al, 1994). CCR8 is found mainly in the thymus (Tiffany HL et al, 1997).
CCR9 (previously called orphan receptor GPR 9-6) is highly expressed in the thymus on both mature and immature T-cells. It is also abundant in T-cells of the intestine but is lowly expressed in lymph nodes and the spleen. Alternative splicing produces two receptors, called CCR9A and CCR9B, CCR9A containing 12 additional amino acids at its N terminus as compared with CCR9B (Yu CR et al, 2000). The A and B forms of the receptor were expressed at a ratio of approximately 10:1. CCR9 has a specific ligand in CCL25 (Thymus-expressed chemokine, TECK) (Zaballos A et al, 1999) and transduces the signal by intracellular calcium mobilization.
CCR10 (previously known as GPR2) (Jarmin DI et al, 2000) is implicated in skin inflammation and recruits regulatory T cells to mucosal layers. CCR10 binds both CCL27 (ESkine, CTACK) (Homey B et al, 2000) and CCL28 (Mucosae-associated epithelial chemokine, MEC) (Wang W et al, 2000) and signal transduction is via increase of intracellular calcium levels.
CCR6 (Baba M et al, 1997) is expressed on inactive memory T-cells and on Th17 cells. CCR6 is down-regulated in activated T-cells. CCL20 (macrophage inflammatory protein 3-alpha, MIP 3-alpha) binds and activates CCR6 and it does not share the binding site of CCR6 with any other chemokine.
Single C motif-1 (SCM-1; lymphotactin, CXC1) is a member of the chemokine receptor family (Yoshida T et al, 1995). CXC differs from the CC chemokines by one amino acid separating two of the four conserved cysteine residues (to give the motif CXC) whereas two adjacent cysteines denote CC. In humans, there are two highly conserved SCM-1 genes, SCYC1 and 2, which encode two SCM-1 proteins, SCM1-alpha and beta (Yoshida T et al, 1996). These proteins act as specific ligands for the CXC1 receptor. This receptor is highly expressed in placenta but lowly in spleen and thymus.
CX3CL1 (fractalkine) is a member of the chemokine superfamily and functions as a human leukocyte chemoattractant protein (Bazan JF et al, 1997). Unlike other human chemokines, the chemokine domain of fractalkine has three amino acids between two conserved cysteines, referred to as the CX3C motif. This molecule can exist in two forms: either membrane-anchored or as a shed 95K glycoprotein. The soluble form has potent chemoattractant activity for T-cells and monocytes, and the membrane-bound protein, which is induced on activated primary endothelial cells, promotes strong adhesion of those leukocytes. The seven-transmembrane high-affinity receptor for fractalkine, termed CX3C1, mediates both the adhesive and migratory functions of fractalkine (Imai T et al, 1997). CX3CL1 is reported to signal via Gi (Brandt et al. 2002).
CXCR6 (formerly called STRL33, BONZO, and TYMSTR) was assigned this name based on its chromosomal location (within the chemokine receptor cluster on human chromosome 3p21) and its similarity to other chemokine receptors in its gene sequence (Liao F et al, 1997). CXCR6 is structurally more closely related to CC chemokine receptors than to other CXC chemokine receptors. It is expressed in lymphoid tissues and activated T cells and is induced in activated peripheral blood lymphocytes. CXCR6 binds the ligand CXCL16 (Shimaoka T et al, 2000) which acts as a scavenger receptor on macrophages. It specifically binds to oxidized low density lipoprotein, suggesting that it may be involved in pathophysiology such as atherogenesis.
CXCR1 (high affinity interleukin-8 receptor A) (Holmes WE et al, 1991) is closely related to CXCR2. They recognize CXC chemokines that possess an E-L-R amino acid motif immediately adjacent to their CXC motif. CXCL8 (interleukin-8, IL-8) (Matsushima K et al, 1988) and CXCL6 (Rovai LE et al, 1997) can both bind CXCR1 in humans and elicit various effects. CXCL8 attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. CXCL6 is a chemotactic factor for neutrophil granulocytes.
CXCR2 (High affinity interleukin-8 receptor B) (Murphy PM and Tiffany HL, 1991) is closely related to CXCR1 and binding of IL-8 to the receptor causes activation of neutrophils. Other ELR-positive chemokines (CXCL1 to CXCL7) can also bind with CXCR2 to cause various effects as described below. CXCL1 (previously known as GRO1 oncogene; NAP-3; MSGA-alpha) (Richmond A et al, 1988) is expressed by neutrophils, macrophages and epithelial cells and possesses neutrophil chemoattractant activity. It is secreted by melanoma cells and is implicated in melanoma pathogenesis. CXCL2 (MIP2-alpha;Gro-beta;Gro-2) (Iida N and Grotendorst GR, 1990; Haskill S et al, 1990) is closely related to CXCL1 (90% amino acid sequence). It is secreted by monocytes and macrophages and attracts polymorphonuclear leukocytes and hematopoietic stem cells. CXCL3 (GRO3; GROg; MIP2-beta) (Haskill S et al, 1990) controls the migration and adhesion of monocytes. CXCL4 (platelet factor 4, PF4) (Poncz M et al, 1987) is released from platelets during aggregation and promotes blood coagulation by neutralization of heparin-like molecules. It is chemotactic for neutrophils, fibroblasts and monocytes. Due to all these roles, CXCL4 is implicated in wound repair and inflammation. CXCL5 (ENA-78) (Walz A et al, 1991) is produced by cells which have been stimulated by interleulin-1 or tumor necrosis factor-alpha. CXCL7 (pro-platelet basic protein, PPBP) (Holt JC et al, 1986) is released from platelets once they are activated. It can stimulate various processes including glucose metabolism, mitogenesis and syntheses of plasminogen activator and extracellular matrix.
The cardiovascular and other actions of the vasoconstricting peptide angiotensin II are mediated by the type 1 and type 2 angiotensin II receptors (AT1 and AT2), which are seven transmembrane glycoproteins with 30% sequence similarity. AT1 receptors (Bergsma DJ et al, 1992) couple to G(q/11), and signal through phospholipases A, C, D, inositol phosphates, calcium channels, and a variety of serine/threonine and tyrosine kinases. The AT2 receptor (Tsuzuki S et al, 1994) is expressed mainly during fetal development. It is much less abundant in adult tissues and is up-regulated in pathological conditions. Its signaling pathways include serine and tyrosine phosphatases, phospholipase A2, nitric oxide, and cyclic guanosine monophosphate. The AT2 receptor counteracts several of the growth responses initiated by the AT1 and growth factor receptors.
G protein-coupled estrogen receptor 1 (GPER; CEPR; G-protein coupled receptor 30, GPR30) (Feng Y and Gregor P, 1997) has a ubiquitous tissue distribution. This orphan receptor is unrelated to nuclear estrogen receptors, but shows all the binding and signaling characteristics of a membrane estrogen receptor (mER). This suggests a role for GPCRs in nonclassical steroid hormone actions.
CXCL12 (stromal cell-derived factor-1, SDF-1) (Shirozu M et al, 1995) is produced in two forms, CXCL12alpha and CXCL12beta, by alternate splicing of the same gene (De La Luz Sierra M et al, 2004). It is a chemoattractant for T-lymphocytes and monocytes, but not neutrophils. In adult humans it plays an important role in angiogenesis by recruiting endothelial progenitor cells from the bone morrow through a CXCR4-dependent mechanism. CXCR4 (fusin) (Herzog H et al, 1993) is the receptor for CXCL12 and, like CCR5, is utilized by HIV-1 to gain entry into target cells. This receptor has a wide cellular distribution, with expression on most immature and mature hematopoietic cell types and also on vascular endothelial cells and neuronal/nerve cells. CXCR7 (RDC-1) (Infantino S et al, 2006) is expressed in monocytes, basophils and B cells and was originally an orphan receptor.
CXCR3 (Loetscher M et al, 1996) is predominantly expressed on T lymphocytes, and on other lymphocytes (some B cells and NK cells). It is highly induced following cell activation. There are three isoforms, CXCR3-A, CXCR3-B and CXCR3-alt. CXCR3 binds to three highly related ligands in mammals, CXCL9, CXCL10 and CXCL11 (Xanthou G et al, 2003). The ligands then elicit their chemoattractant functions. CXCL9 (CMK; monokine induced by gamma-interferon, MIG; SCYB9) is a T cell chemoattractant (Farber JM, 1993). CXCL10 (IP-10) (Booth V et al, 2002) is secreted by monocytes, endothelial cells and fibroblasts in response to gamma-interferon. It can act as a chemoattractant for monocytes, macrophages, T cells, NK cells and dendritic cells, promote T cell adhesion to endothelial cells and inhibit angiogenesis and bone marrow colony formation. CXCL11 (I-TAC,; iIP-9) (Cole KE et al, 1998) is highly expressed in peripheral blood leukocytes, pancreas and liver. It is regulated by interferon and has potent chemoattractant activity for interleukin-2-activated T cells.
The Duffy blood group system consists of two antigens defining four phenotypes (Marsh WL, 1975). Duffy antigen/receptor for chemokines (DARC) (Chaudhuri A et al, 1993) carries the Duffy (Fy) blood group and acts as a widely expressed promiscuous chemokine receptor. The chemokine interleukin-8 is one example shown here.
There are three well-characterized families of opioid peptides produced by the body: endorphins, enkephalins and dynorphins. Endorphins are processed from the precursor proopiomelanocortin (POMC) (Takahashi H et al, 1981), which can also be processed to yield adrenocorticotropic hormone (ACTH) and alpha- and gamma-melanocyte stimulating hormone (MSH). Beta-endorphin (Dragon N et al, 1977) is a 31 amino acid peptide found in neurons of the hypothalamus and pituitary gland. It is released into the blood (from the pituitary gland) and into the spinal cord and brain from hypothalamic neurons during vigourous exercise, excitement and orgasm. Beta-endorphin binds with the highest affinity to the mu-opioid receptor but it also possesses some affinity towards the delta- and kappa-opioid receptors. Once bound, it acts as an analgesic in the body by dulling pain. It does this by breaking down bradykinins which are peptides which accumulate in response to injury. The mu-opioid receptor (MOR) (Wang JB et al, 1994) possesses high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. The enkephalins are endogenous ligands, or specifically endorphins, as they are internally derived and bind to the body's opioid receptors. There are two forms of enkephalin, one containing leucine ("leu"), while the other contains methionine ("met"). The met-enkephalin peptide sequence is coded by the POMC gene whereas leu-enkephalin is coded by both POMC and dynorphin genes. Enkephalins are pentapeptides involved in regulating pain and nociception in the body. Their action is mediated through the delta-opioid receptor (DOR) (Knapp RJ et al, 1994). Dynorphins constitute a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released, amongst which are dynorphin A, dynorphin B, big-dyn and alpha/beta-neoendorphin (Day R et al, 1998). Dynorphins primarily exert their effects through the kappa-opioid receptor (KOR), a G-protein coupled receptor (Simonin F et al, 1995). Two subtypes of KORs have been identified: K1 and K2. Although KOR is the primary receptor for all dynorphins (James IF et al, 1982), the peptides do have some affinity for MOR and DOR.
Bradykinin (Rocha e Silva M, et al, 1949) is a 9 amino-acid peptide belonging to the kinin group of proteins. It causes blood vessel dilation via the release of prostacyclin, nitric oxide and endothelial-derived hyperpolarizing factor, resulting in lower blood pressure. It is also involved in the pain mechanism. Bradykinin exerts its effects through two receptors, bradykinin receptor B1 and 2 (B1R and B2R respectively). B1R (Menke JG et al, 1994) is synthesized de novo following tissue injury and receptor binding leads to an increase in cytosolic calcium concentration, resulting in chronic and acute inflammatory responses. Unlike B1R, B2R (Hess JF et al, 1992) is ubiquitously and constitutively expressed in healthy tissues. It also increase cytosolic calcium concentration and stimulates the mitogen-activated protein kinase pathways.
Apelin (Tatemoto K et al, 1998) is an endogenous ligand for the apelin (APJ) receptor (O'Dowd BF et al, 1993) and is widely expressed in the human body including the heart and brain. Apelin is one of the most potent stimulators of cardiac contractility and mediates blood pressure and blood flow. Several active peptides can be produced by proteolytic processing of the peptide precursor (apelin-36, 31, 28 and 13). APJ is related to the angiotensin receptor (40-50% identity) and couples to G proteins that inhibit adenylate cyclase activity. It is an alternative coreceptor with CD4 for HIV-1 infection. Binding of apelin to its receptor inhibits HIV-1 entry in cells coexpressing CD4 and APJ.
The orphan nociceptin (ORL1) receptor (Mollereau C et al, 1994) is most closely related to opioid receptors on structural (sequence) and functional grounds but is not a typical opioid receptor. It may play a role in instinctive behaviours and emotions. Its natural ligand is nociceptin (orphanin FQ) (Mollereau C et al, 1996), a 17 amino acid neuropeptide which acts as a potent anti-analgesic. Both receptor and ligand are widely expressed in the CNS.
Somatostatin (growth hormone inhibiting hormone, GHIH; somatotropin release-inhibiting factor, SRIF) (Shen LP et al, 1992) is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with somatostatin receptors 1-5 (Hoyer D et al, 1995). Somatostatin has two active forms produced by alternative cleavage of the single preproprotein and named according to the number of amino acids in the chain; Somatostatin-28 and somatostatin-14. The 5 receptors known to date all couple with pertussis toxin-sensitive G proteins to inhibit adenylate cyclase after ligand binding. They were classified according to the dates they were discovered; SSTR1 and 2 (Yamada Y et al, Jan. 1992), SSTR3 (Yamada Y et al, Dec. 1992) and SSTR4 and SSTR5 (Yamada Y et al, Sep. 1993).
The structurally related (70% identity) orphan G-protein-coupled receptors, neuropeptides B/W receptor 1 and 2 (GPR7 and GPR8 respectively) (O'Dowd BF et al, 1995), are wideley expressed in the central nervous system of humans. Natural ligands identified for these receptors are involved in the regulation of feeding. Neuropeptide B is cleaved into two chains; NPB23 (L7) and NPB29 (L7C). Neuropeptide W is also cleaved into two chains; NPW23 (L8) and NPW30 (L8C) (Tanaka H et al, 2003). Both these peptides can bind to either GPR7 or 8 to elicit their effects downstream.
Bombesin-like receptors are widely distributed in the CNS as well as in the GI tract where they modulate smooth-muscle contraction, exocrine and endocrine processes, metabolism, and behaviour through the binding of bombesin-like peptides. They include gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R) (Corjay MH et al, 1991) and bombesin-like receptor-3 (BRS-3) (Fathi Z et al, 1993). BRS-3 binds bombesin peptides with low affinity and is often classed as an orphan receptor. There are two homologues of bombesin-like peptides; Gastrin-releasing peptide (GRP) (Sausville EA et al, 1986) and Neuromedin-B (NMB) (Krane IM et al, 1988). GRP regulates gastric acid secretion and motor function and is a negative feedback operator regulating fear. NMB is involved in the regulation of many functions such as cell growth, body temperature and blood pressure and glucose levels.
C5a (Fernandez HN and Hugli TE, 1978) is a protein fragment released from complement component C5. C5a is a potent anaphylatoxin, causing the release of histamine from mast cells and also being an effective leukocyte attractant. The C5a receptor (complement component 5a receptor 1, C5AR1; Cluster of Differentiation 88, CD88) (Gerard NP and Gerard C, 1991) mediates the pro-inflammatory and chemotactic actions of C5a.
Substance P (Harmar AJ et al, 1986) is an neuropeptide, 11 amino-acids in length, that acts as a neurotransmitter for pain response neurons. It does this by binding to its endogenous receptor neurokinin 1 (NK1R, substance P receptor) which belongs to the tachykinin receptor sub-family of GPCRs (Takeda Y et al, 1991).
Neurokinin A (substance K) (Gerard NP et al, 1990) is a peptide neurotransmitter of the tachykinin family which can act as a mediator in human airway and gastrointestinal tissues. Neurokinin A acts via the substance K receptor (NK-2 receptor) (Harmar AJ et al, 1986), believed to be localized on smooth muscle cells and pharmacologically coupled to a GTP-binding protein.
Neurokinin B peptide (NKB) (Torricelli M et al, 2007) is a tachykinin-related neuropeptide that is highly expressed in the placenta.It can bind to its receptor, NK3 (Huang RR et al, 1992), which is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. Elevated levels of NKB in early pregnancy may be an indicator of hypertension and pre-eclampsia (Page NM et al, 2000), and treatment with certain neurokinin receptor antagonists may be useful in alleviating the symptoms.
In humans there are three main arginine vasopressin receptors; AVPR1A, 1B and 2. AVPR1A (Thibonnier et al. 1994) and AVPR1B (Sugimoto et al. 1994) act as receptors for the signal peptide Arg-vasopressin (AVP(20-28)), a cleaved peptide from the precursor AVP protein (Mohr et al. 1985, Sausville et al. 1985) and are expressed mainly in the brain. The 1A and 1B forms use G protein alpha q/11 subunits as their second messenger system.
Oxytocin is a nonapetide closely related to vasopressin (Mohr E et al, 1985; Sausville E et al, 1985). It is best known for its roles in female reproduction: it is released in large amounts during labour facilitating birth and afterwards, breastfeeding. It also acts as a neurotransmitter in the brain. The actions of oxytocin via the oxytocin receptor (Kimura T et al, 1992) are mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system.
Cholecystokinin (CCK, previously called pancreozymin) (Takahashi Y et al,1985) is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein. CCK is synthesized by I-cells in the small intestine and secreted in the duodenum, causing the release of digestive enzymes and bile from the pancreas and gall-bladder respectively. It also acts as a hunger suppressant. CCK receptors bind CCK. In humans, there are two receptor types, A (Ulrich CD et al, 1993) and B (Pisegna JR et al, 1992). The A type are primarily distributed in the GI tract whereas the B type are primarily in the CNS. In the CNS, type B receptors modulate anxiety, analgesia, arousal, and neuroleptic activity.These receptors mediates the action of CCK by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Endothelins are 21-amino acid vasoconstricting peptides produced primarily in the endothelium that play a key role in vascular homeostasis. An imbalance and over-expression of endothelins can contribute to hypertension (high blood pressure). Endothelins are implicated in vascular diseases of several organ systems, including the heart, general circulation and brain. There are 3 isoforms designated ET1, ET2 and ET3 (Inoue A et al, 1989).
These bind to two receptors, designated ETA (Adachi M et al, 1991) and ETB (Nakamuta M et al, 1991). ETA receptors are primarily located in smooth muscle of blood vessels. Endothelin binding to ETA causes vasoconstriction and sodium retention, leading to increased blood pressure. ETB are primarily located on endothelial cells lining the internal walls of vasculature. Endothelin binding to ETB leads to the release of NO (nitric oxide) which is a strong vasodilator.
Melanocortins are a group of pituitary peptide hormones that include corticotropin (ACTH) and the alpha, beta and gamma melanocyte-stimulating hormones (MSH) derived from the prohormone proopiomelanocortin (Takahashi H et al, 1981). Melanocortins can act through multiple melanocortin receptors (MC1R-MC5R) (Mountjoy KG et al, 1992). The majority of melanocortin receptors (MC1R, MC3R, MC4R and MC5R) are semi-selective in their ability to bind multiple melanocortins (MSH and ACTH). MSH regulates pigmentation.
MC2R (aka ACTH receptor) selectively binds POMC(138-176) (ACTH, corticotropin) (Gantz et al. 1993, Lee et al. 1961, Mountjoy et al. 1992). ACTH regulates adrenal cortical function via the G protein alpha-s subunit.
The prolactin-releasing peptide receptor (PrRP; GRP10) (Marchese A et al, 1995) is expressed in the pituitary gland (Fujii R et al, 1999) and binds prolactin-releasing peptide (PrRP) (Hinuma S et al, 1998). PrRP is implicated in lactation, regulation of food intake and pain-signal processing. Human PrRP-20 failed to alter basal or forskolin-stimulated levels of intracellular cyclic AMP in HEK293-GPR10 cells, suggesting that GPR10 does not couple via either Gs or Gi (Langmead et al. 2000).
At least four neuropeptide Y receptor subtypes each with specific affinities to neuropeptide Y peptides, serve as regulators of mucosal function, gastrointestinal motility and secretion. Four receptors have been characterized to date; NPY1R (Larhammar D et al, 1992), NPY2R (Gerald C et al, 1995), NPY4R (Bard JA et al, 1995) and NPY5R (Parker EM and Xia L, 1999).
Neuropeptide Y peptides are also implicated as mediators in the pathogenesis of many gastrointestinal disorders, including malabsorption, short gut, inflammatory bowel diseases, and forms of pancreatitis. The three peptides are neuropeptide Y (NPY) (Minth CD et al, 1984), peptide YY (PYY) (Tatemoto K et al, 1988) and pancreatic peptide (PP) (Boel E et al, 1984).
Although each peptide can bind to any of the four receptors, they each have preferred receptors. NPY binds preferentially to NPY1R, PYY to NYP2R and PP to NYP4R.
Neurotensin (Dong Z et al, 1998) is a 13-amino acid neuropeptide that is implicated in the regulation of luteinizing hormone and prolactin release. It also has significant interaction with the dopaminergic system. Neurotensin is synthesized as part of a precursor protein that also contains the related neuropeptide neuromedin N. The neurotensin receptor binds neurotensin. There are two transmembrane receptors encoded by the NTSR1 (Vita N et al, 1993) and NTSR2 (Vita N et al, 1998) genes.
The KiSS1-derived peptide receptor, GPR54 is a galanin-like GPCR (Lee DK et al, 1999) that can bind kisspeptin-54 (metastin), a natural ligand of the receptor (Kotani M et al, 2001). The GPR54 gene appears to be essential for normal puberty and gonadotropin-released hormone physiology (Seminara SB et al, 2003). Metastin is encoded by the KiSS-1 metastasis suppressor gene, a 54-amino acid peptide that suppresses metastases of human melanomas and breast carcinomas without affecting tumorigenicity (Ohtaki T et al, 2001).
Galanin is a 30-amino acid inhibitory neuropeptide encoded by the GAL gene (Schmidt WE et al, 1991; Bersani M et al, 1991). It is involved in a number of physiological processes such as regulation of food intake, metabolism and reproduction and regulation of neurotransmitter and hormone release. These actions are mediated via the galanin receptor which binds galanin. Three receptor subtypes exist; GALR1 (Habert-Ortoli E et al, 1994), GALR2 (Fathi Z et al, 1998; Kolakowski LF et al, 1998) and GALR3 (Smith KE et al, 1998; Kolakowski LF et al, 1998). These receptors are found throughtout the PNS, CNS and the endocrine system.
The orphan QRFP receptor (SP9155) (Lee DK et al, 2001) shares a high sequence homology with the neuropeptide FF receptor. It mediates the activity of neuropeptide QRFP (Jiang Y et al, 2003), which is suspected to have orexigenic activity, via the G alpha-q/11 subunit (Langmead CJ et al, 2000).
Thrombin (Butkowski RJ et al, 1977) plays a vital role in blood homeostasis, inflammation and wound healing. Thrombin (which cleaves bonds after arginine and lysine) converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII. Complexed with thrombomodulin it can also activate protein C. It performs these functions by binding to four proteinase-activated receptors (PAR1-4) (Kahn ML, et al, 1999; Bohm SK et al, 1996). These complexes couple to G proteins which stimulate phosphoinositide hydrolysis.
The orexin (hypocretin) neuropeptides (A and B) both derive from a 131 residue precursor, prepro-orexin peptide (Sakurai T et al, 1999). Orexin A (Takai T et al, 2006) binds preferentially to the orphan GPCR orexin 1 receptor (Sakurai T et al, 1998). This activated complex can transduce its signal via the Gq class of G protein.
The orexin (hypocretin) neuropeptides (A and B) both derive from a 131 residue precursor, prepro-orexin peptide (Sakurai T et al, 1999). Orexin B (Lee JH et al, 1999) binds preferentially to the orphan GPCR orexin 2 receptor (Sakurai T et al, 1998). This activated complex can transduce its signal via the Gq class of G protein. Orexin deficiency is inferred in narcolepsy and regulation of feeding behaviour.
The 8 residue neuropeptide FF (NPFF, morphine-modulating peptide) (Perry SJ et al, 1997) is believed to play a role in pain modulation and opiate tolerance. Two G protein-coupled receptors bind NPFF; NPFF1 and NPFF2 (Bonini JA et al, 2000). These receptors share the highest amino acid sequence homology with members of the orexin, NPY, and cholecystokinin families, which have been implicated in feeding. This may be a potential role for NPFF1/2. These receptors mediate the action of NPFF by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
The alpha-1 adrenoceptors are involved in smooth muscle contraction. This is achieved by the receptor-ligand complex coupling with the G protein alpha-q/11 subtype, which results in increased intracellular calcium and thus muscle contraction. There are 3 subtypes of the alpha-1 adrenoceptor; 1a (Hirasawa A et al, 1993), 1b (Ramarao CS et al, 1992) and 1d (Esbenshade TA et al, 1995).
The M1 receptor (Peralta EG et al, 1987) is found in exocrine glands and the CNS. It mediates slow excitatory postsynaptic potential (EPSP) at the ganglion in the postganglionic nerve. The M3 receptor (Peralta EG et al, 1987) is found in smooth muscle of the blood vessels and in the lungs. M3 mediates vascular relaxation (by activating vascular endothelial cells causing increased NO synthesis) and lung constriction (by coupling to Gq protein causing increased intracellular calcium). The location of the M5 receptor is not well known but thought to be in the CNS. All of these three receptors couple with Gq/11 protein which use the upregulation of phospholipase C and therefore inositol trisphosphate and intracellular calcium as a signaling mechanism (Bräuner-Osborne H and Brann MR, 1996).
Alpha-2 adrenoceptors couple with G protein alpha-i subtype which decreases adenylyl cyclase activity, thus reducing cAMP intracellular levels resulting in smooth muscle contraction. There are three alpha-2 subtypes in humans; 2A (Kobilka BK et al, 1987), 2B (Weinshank RL et al, 1990) and 2C (Hirasawa A et al, 1993).
M2 muscarinic receptors (Peralta EG et al, 1987) are located in the heart, where they act to slow the heart rate down to normal sinus rhythm after stimulatory actions of the sympathetic nervous system. This is achieved by slowing the speed of depolarization. M4 muscarinic receptors are expressed in the CNS (Peralta EG et al, 1987). Both receptors act via Gi proteins, causing a decrease in cAMP in the cell and generally leading to inhibitory-type effects (Bräuner-Osborne H and Brann MR, 1996).
Beta adrenoceptors couple with G protein alpha-s subtype (Wenzel-Seifert K et al, 2002), increasing cAMP activity resulting in heart muscle contraction, smooth muscle relaxation and glycogenolysis. There are three subtypes in humans; beta1 (Frielle T et al, 1987), beta2 (Kobilka BK et al, 1987) and beta 3 (Emorine LJ et al, 1989).
Dopamine receptors 1 (Dearry A et al, 1990) and 5 (Sunahara RK et al, 1991) are members of the D1-like dopamine receptor family. Once activated, they couple to the G protein alpha-s subtype which can activate adenylate cyclase. This increases the intracellular concentration of cAMP, which, in neurons, is typically excitatory.
Dopamine receptors 2 (Grandy DK et al, 1989), 3 (Giros B et al, 1990) and 4 (Van Tol HH et al, 1991) are members of the D2-like dopamine receptor family. Once activated, these receptors couple with the G protein alpha-i subtype which directly inhibits cAMP formation by inhibition of the enzyme adeylate cyclase.
Histamine H3 receptor (Lovenberg TW et al, 1999) is predominantly expressed in the CNS and is involved in decreasing the release of neurotransmitters such as histamine, acetylcholine, norepinephrine and serotonin. There are currently at least six isoforms of the H3 receptor in humans of which isoforms 1,2 and 4 encode functional proteins (Wellendorph P et al, 2002). Histamine H4 receptor (Nakamura T et al, 2000) is highly expressed in bone marrow and white blood cells. It is also found in other tissues such as colon, liver, lungs and thymus. The H4 receptor mediates mast cell chemotaxis. Both the H3 and H4 receptors mediate their actions by coupling with the G protein alpha-i subtype, thus decreasing intracellular cAMP.
Histamine H2 receptors (Gantz I et al, 1991) are primarily located on parietal cells (oxyntic cells) which are the stomach epithelium cells that secrete gastric acid in response to histamine. This action is modulated by coupling of the activated receptor with the G protein alpha-s subtype which can stimulate adenylate cyclase (Mitsuhashi M et al, 1989). Through a separate mechanism, the activated receptor can also couple with the G protein alpha-q/11 to stimulate phospholipase C (Mitsuhashi M et al, 1989). H2-receptor antagonists (H2RA) are a class of drugs used to block the action of histamine on parietal cells in the stomach, decreasing the production of acid by these cells.They are used in the treatment of dyspepsia.
The histamine H1 receptor (De Backer MD et al, 1993) is found on smooth muscle, endothelium and the CNS. Histamine released from neurons binds to the H1 receptor and causes systemic vasodilation and increased endothelial cell permeability. The effects are modulated by the activated receptor binding to the G protein alpha-q/11 subtype which can activate phospholipase C and the phosphatidylinositol (PIP2) signaling pathway (Tilly BC et al, 1990). The classical antihistamines (histamine H1 receptor antagonists) were developed in the early 1930s and were shown to reduce the effects of histamine on many tissues.
5-HT1 receptors, once bound to serotonin (5-HT), act on the CNS where they induce neuronal and presynaptic inhibition and behavioural effects. In humans, there are five subtypes of the 5-HT1 receptor, designated 1A-1F (there is no 1C type) (Stam NJ et al, 1992; Hamblin MW et al, 1992; Weinshank RL et al, 1992; Zgombick JM et al, 1992; Adham N et al, 1993). 5-HT5A is expressed in human brain (Rees S et al, 1994) and has an inhibitory effect like 5-HT1 receptors. Both these subtypes mediate their actions by coupling with the G protein alpha-i/o subtype (Lin SL et al, 2002; Francken BJ et al, 1998), inhibiting adenylate cyclase activity and thus decreasing celular cAMP levels.
The 5-HT-2 receptors mediate many of the central and peripheral physiologic functions of serotonin. There are three subtypes; 2A (Stam NJ et al, 1992), 2B (Kursar JD et al, 1994; Schmuck K et al, 1994) and 2C (Stam NJ et al, 1994). The actions of these receptors are mediated by coupling with the G protein alpha-q/11 subtype which activates phospholipase C, increasing cellular levels of inositol trisphosphate (IP3) and diacylglycerol (DAG) (Lucaites VL et al, 1996).
The 5-HT4 receptor (Van den Wyngaert I et al, 1997) is located in the alimentary tract, bladder, heart and adrenal gland as well as the central nervous system (CNS). It modulates the release of various neurotransmitters. Multiple transcripts encode proteins with distinct C-terminal sequences, but the full-length nature of some transcript variants has not been determined (Blondel O et al, 1998). The 5-HT6 receptor (Kohen R et al, 1996) is primarily expressed in the brain and is involved in glutamatergic and cholinergic neuronal activity. The 5-HT7 receptor (Stam NJ et al, 1997) plays a role in vasculature smooth muscle relaxation and in the GI tract. It is involved in thermoregulation, circadian rhythm, learning and memory, and sleep. All these receptor types mediate their actions by coupling to the G protein alpha-s subtype, which increases cellular cAMP levels (Baker LP et al, 1998; Zhang JY et al, 2003).
Trace amines, such as para-tyramine, beta-phenylethylamine (beta-PEA) and tryptamine are endogenous sympathomimetics. They are related to classical biogenic amines such as histamine, serotonin and catecholamines. The trace amine receptor TAR1 was identified in rat (Borowsky et al. 2001; Bunzow et al. 2001) and recognized to be a member of a family of trace amine-associated receptors (TAARs). Humans have seven subtypes plus a number of pseudogenes (TAAR1,2,3,5,6,8 and 9). Only one of these has been demonstrated to respond to trace amines, TAAR1. These receptors mediate their actions by coupling with the G protein alpha-s subtype, which activates adenylate cyclase and elevates cellular cAMP levels. Beta-PEA is the trace amine used as an example in this annotation.
Luteinizing hormone releasing hormone (LHRH, also termed gonadotropin releasing hormone GnRH), is a decapeptide involved in the control of human reproduction. There are two genes, LHRH I and II which encode two hormones (Seeburg PH and Adelman JP, 1984; White RB et al, 1998). They are produced by hypothalamic neurones and mediates the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from gonadotropic cells in the anterior pituitary. Their effects are mediated by binding to the gonadotropin-releasing hormone receptors 1 and 2 (GnRHR) (Kakar SS et al, 1992; Faurholm B et al, 2001) which couple with the G protein alpha-q/11 subunit.
Thyroid-stimulating hormone (TSH, thyrotropin) is a dimeric glycoprotein synthesized and secreted by thyrotrope cells in the anterior pituitary gland. TSH regulates the endocrine function of the thyroid gland, mediating the release of the hormones thyroxine (T4) and triiodothyronine (T3).
Thyrostimulin is a dimer of Glycoprotein hormone alpha-2 (GPHA2) and Glycoprotein hormone beta-5(GPHB5), comprising the a fifth glycoprotein hormone (Nakabayashi et al. 2002), a more potent ligand for the TSH receptor than TSH which has a wider tissue distribution (Huang et al. 2016).
These effects are mediated by the TSH receptor (Nagayama Y et al, 1989), found primarily on thyroid follicular cells. The activated receptor couples with the G protein alpha-s subunit (Allgeier A et al 1994) which activates adeylate cyclase and increases intracellular cAMP levels.
Luteininzing hormone (LH, lutropin) is a dimeric glycoprotein synthesized in the anterior pituitary gland. It triggers ovulation in females and stimulates Leydig cell production of testosterone in males. It mediates its action by binding to the LH receptor (Minegishi T et al, 1990, Jia XC et al, 1991), which is found in the ovary, testes and uterus. The activated receptor couples to the G protein alpha-s subunit (Gilchrist RL et al, 1996) which activates adenylate cyclase and increases intracellular cAMP levels.
Follicle-stimulating hormone (FSH) is a dimeric glycoprotein hormone synthesized and secreted by gonadotropes in the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the human body. The actions of FSH are mediated by the FSH receptor (Minegishi T et al, 1991), found in the ovaries, testes and uterus. Once activated, the receptor mediates its action by coupling to the G protein alpha-s subunit (Timossi C et al, 2002), which activates adenylate cyclase and increases intracellular cAMP levels.
Oxoeicosanoids are a family of biologically active arachidonic acid derivatives that are associated with cellular migration. These mediators are potent chemotaxins for eosinophils, monocytes and polymorphonuclear neutrophils. They act via the OXE receptor (Hosoi T et al, 2002), expressed principally in kidney, liver as well as in eosinophils, neutrophils, and lung macrophages. The most potent ligand is 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE). Activation of the receptor leads to calcium mobilization and the receptor was shown to be coupled to the G alpha i subunit (Jones CE et al, 2003).
The N-formyl peptide receptor 2 (FPR2, LXA4 receptor, FPRL1) (Ye et al. 1992, Fiore et al. 1994) has been reported to respond to numerous ligand with a broad range of structural diversity (Migeotte et al. 2006). It was originally identified as a low-affinity receptor for N-formyl-methionyl peptides but has greater affinity for many ligands including lipoxin A4 (Fiore et al. 1994, Migeotte et al. 2006), annexin-1 (Perretti et al. 2002), the truncated chemokine sCKbeta8-1 (Elagoz et al. 2004) and humanin (Ying et al. 2004).
EP3 receptor mRNA are subject to alternative splicing at their 3'-ends and, to date, six expressed protein isoforms have been found in man (Yang J et al, 1994; Schmid A et al, 1995). These isoforms (not annotated here) differ in their G-protein coupling thereby contributing to the wide spectrum of EP3 actions: contraction of smooth muscle, enhancement of platelet aggregation, inhibition of autonomic neurotransmitter release, inhibition of gastric acid secretion, and inhibition of fat cell lipolysis.
G protein-coupled receptor 44 (GPR44) is a GPCR that has recently been found to belong to the prostanoid receptor family and named DP2 (CRTH2) (Marchese A et al, 1999). The effects of PGD2 bound to the receptor are mediated by coupling with the G protein alpha i/o subunit which inhibits cAMP production (Sawyer N et al, 2002).
DP1 is a G-protein-coupled receptor encoded by the PTGDR gene (Boie Y et al, 1995). Its activity is mainly mediated by the G protein alpha s subunit that stimulates adenylate cyclase resulting in an elevation of intracellular cAMP and Ca2+ (Seiler S et al, 1990).
The EP1 protein (Funk CD et al, 1993) is one of four receptors identified for prostaglandin E2 (PGE2). The effects of PGE2 are mediated through the G protein g alpha q/11 subunits and the subsequent phosphatidylinositol-calcium second messenger system (Funk CD et al, 1993).
In general, nucleotides and cysteinyl-leukotrienes (CysLTs) are unrelated signaling molecules inducing multiple effects via separate G-protein-coupled receptors: the purinoceptors and CysLT receptors. However, GPR17, an orphan receptor at intermediate phylogenetic position between P2Y and CysLT receptors, is specifically activated by both families of endogenous ligands. The orphan receptor GRR17 has been identified as a dual uracil nucleotide/cysteinyl-leukotriene receptor (Ciana P et al, 2006). Here, the ligands cys-LTs bind with the receptor and their effects are mediated by coupling to the G protein alpha i subunit (Ciana P et al, 2006).
Thromboxane (TBXA2) is a potent stimulator for platelet aggregation and clot formation and also plays a role in vascular tone. The thromboxane receptor TP (Hirata et al. 1991) is found on the surface of vascular endothelium, platelets and in the placenta. Once bound to its ligand, TP's effects are mediated via coupling to G q/11 activation of a phosphatidylinositol-calcium second messenger system (Kinsella BT et al, 1997). TP signaling also involves G12/13 signaling; selective activation of G12/13 results in dense granule release in a mechanism that is independent of Gq/phospholipase C. The downstream mechanism for this is thought to be RhoA mediated activation of PKCdelta, as PAR-mediated dense granule release is inhibited if RhoA is blocked, and RhoA regulates PKCdelta T505 phosphorylation (Jin et al. 2009).
Once activated by PGE2, the EP2 (Regan JW et al, 1994) receptor:ligand complex can mediate downstream effects by coupling to the G protein alpha s subunit and activate adenylyl cyclase (Schwaner I et al, 1995). EP4 receptors (Bastien L et al, 1994) are present on smooth muscle cells and their effects are mediated via coupling to G protein alpha s subunit and subsequent stimulation of adenylate cyclase (Wilson RJ et al, 2004).
The dihydroxy-leukotriene, leukotriene B4 (LTB4) stimulates neutrophil chemotaxis and secretion. Chemotaxis, the principal effects of LTB4 and related dihydroxy-acids on leukocytes, occurs via activation of BLT (1 and 2) receptors (Yokomizo T et al, 1997; Yokozimo T et al, 2000). BLT2 is expressed ubiquitously, in contrast to BLT1, which is expressed predominantly in leukocytes. These receptors mediate their actions by coupling to G protein alpha q/11 subunits (McLeish KR et al, 1989) which activate a phosphatidylinositol-calcium second messenger system.
Prostacyclin (PGI2) prevents formation of the platelet plug involved in primary hemostasis (a part of blood clot formation) and is an effective vasodilator. Binding to its receptor (IP, PTGIR) (Boie et al. 1994) allows coupling to and activation of the G protein alpha s subunit, which leads to activation of cAMP and increase in protein kinase A (PKA) activity (Schwaner et al. 1995).
The cysteinyl-leukotrienes (cys-LTs) are potent smooth muscle contractile agents mediating bronchoconstriction. Examples are LTC4, LTD4 and LTE4. There are two human cys-LT receptors, 1 (Lynch KR et al, 1999) and 2 (Heise CE et al, 2000). They mediate their effects via coupling to the G protein alpha q/11 subunit (Sarau HM et al, 1999).
Arginine vasopressin receptor 2 (AVPR2) (Birnbaumer et al. 1992) is expressed in the kidneys and can bind the signal peptide Arg-vasopressin (AVP(20-28)), a cleaved peptide from the precursor AVP protein (Mohr et al. 1985, Sausville et al. 1985). This receptor uses the G protein alpha s subunit as its second messenger system.
Prostaglandin F receptor (FP) is a GPCR for Prostaglandin F2alpha and is encoded by the PTGFR gene (Abramovitz M et al, 1994). Main effects of prostaglandin binding to the receptor are uterine contraction and bronchoconstriction. These effects are mediated by coupling with the G protein alpha q/11 subunit which activates a phosphatidylinositol-calcium second messenger system (Carrasco MP et al, 1997).
The human form of the receptor was cloned and sequenced as GPR23 (Janssens R et al, 1997). P2Y9 has been reported to bind lysophosphatidic acid (LPA) as a ligand and elicit numerous effects via multiple G proteins (Lee CW et al, 2007).
The P2Y11 receptor (Communi D et al, 1997) can bind adenosine nucleotides but not uridine nucleotides. This receptor is coupled to the stimulation of both the phosphoinositide (Gq/11) and adenylyl cyclase (Gs) pathways (Qi AD et al, 2001).
P2RY12 (Bodor et al. 2003) is found on the surface of blood platelet cells and is an important regulator in blood clotting. It is one of two ADP receptors expressed in platelets, the other is P2RY1. Activation leads to irreversible platelet aggregation. Defects in this receptor are associated with bleeding disorders. Its preferred ligand is ADP. The platelet anticoagulant drug clopidogrel binds to this receptor (Hollopeter G et al. 2001).
The P2Y10 receptor is expressed during myeloid differentiation of HL60 cells (Adrian K et al, 2000) and is the first dual lysophospholipid receptor, able to bind both sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) (Murakami M et al, 2008). The effects of this receptor are mediated by coupling with the G protein alpha q/11 subunit.
Uridine 5'-diphosphoglucose (UDP-glucose) has a well established biochemical role as a glycosyl donor in the enzymatic biosynthesis of glycogen and polysaccharides. UDP-glucose may also possess pharmacological activity and is found to activate the orphan receptor P2Y14 (KIAA0001) (Chambers JK et al, 2000). Nucleotides known to activate P2Y receptors were inactive towards P2Y14. This receptor's actions are mediated by coupling with the G protein alpha Gi/o which inhibits adenylyl cyclase and thus, reduces cAMP accumulation (Fricks IP et al, 2009).
The P2Y5 receptor (Lee CW et al, 2006) binds lysophosphatidic acid (LPA). Its effects are mediated by coupling with the G protein alpha G q/11 and G12/13 subunits (Lee CW et al, 2006). Mutations in the P2RY5 gene cause a rare, inherited form of hair loss called Hypotrichosis simplex. It is the first receptor in humans known to play a role in hair growth (Pasternack SM et al, 2008).
The P2Y6 receptor (Communi D et al, 1996) is responsive to UDP, partially responsive to UTP and ADP, and not responsive to ATP. Four transcript variants encoding the same isoform have been identified for this gene. The effects of P2Y6 are mediated by coupling to stimulation of both the phosphoinositide and adenylyl cyclase pathways, a unique feature among the P2Y family (Communi D et al,1997).
P2RY1 binds ADP (Leon et al. 1996). It is one of two platelet ADP receptors, the other is P2RY12, that initiate platelet activation when stimulated in concert. P2RY1 signals through Gq, while P2Y12 signals through Gi. This results in mobilization of intracellular calcium ions via activation of phospholipase C, which leads to a change in platelet shape and probably to platelet aggregation (Schachter et al. 1997).
The P2Y2 receptor (Parr CE et al, 1994) is responsive to both adenosine and uridine nucleotides. It may participate in control of the cell cycle of endometrial carcinoma cells. Three transcript variants encoding the same protein have been identified for this gene. The effects of P2Y2 are mediated by coupling with the G protein alpha Gq/11 subunits (Schachter JB et al, 1997). P2Y2 is a potential drug target for treating cystic fibrosis (Kellerman D et al, 2002).
The A1 receptor (Libert F et al, 1992) has an inhibitory function on most of the tissues in which it is expressed. In the brain, it slows metabolic activity and also decreases heart rate. The A1, together with A2a receptors, are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow. The A3 receptor (Salvatore CA et al, 1993) mediates a sustained cardioprotective function during cardiac ischemia and it is involved in the inhibition of neutrophil degranulation in neutrophil-mediated tissue injury. Both the A1 and A3 receptors mediate their effects by coupling with the G protein alpha i subunit which inhibits adenylyl cyclase (Wise A et al, 1999).
GPR17, an orphan receptor at intermediate phylogenetic position between P2Y and CysLT receptors, is specifically activated by both families of endogenous ligands, leading to both adenylyl cyclase inhibition and intracellular calcium increases. In this example, GPR17 binds to UDP. The UDP-bound receptor couples with Gq/11 and leads to intracellular calcium increases (Ciana P et al, 2006).
Adenosine receptors A2a and A2b (ADORA2A and ADORA2B) bind extracellular adenosine (Ado-Rib) and are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow (Peterfreund 1996). The A2A receptor is responsible for regulating myocardial blood flow by vasodilation of the coronary arteries, which increases blood flow to the myocardium, but may lead to hypotension. Just as in A1 receptors, this normally serves as a protective mechanism. A2B receptor work (Pierce KD et al, 1992) has lagged behind research in the other adenosine receptors. Both ADORA receptors mediate their actions by coupling with the G protein alpha s subunit which activates adenylyl cyclase and increases intracellular cAMP concentrations. In surfactant physiology, the receptor:adenosine complex positively regulates surfactant export from lamellar bodies. (Cooper JA et al, 1995; Linden J et al, 1999). Adenosine deaminase (CECR1, ADA2) degrades extracellular adenosine (Ade-Rib), reducing or neutralising the positive regulatory effect of adenosine in surfactant export.
Melatonin (N-acetyl-5-methoxytryptamine) is a natural hormone produced by the pineal gland that is involved in the regulation of circadian rhythms. These actions are mediated by melatonin receptors. Melatonin can also function as a powerful antioxidant in the protection of nuclear and mitochondrial DNA.There are two melatonin receptors in humans, MT1 (Mel1a, MTNR1A) and MT2 (Mel1b, MTNR1B). Their actions are mediated by coupling with the G protein alpha i/o subunits to inhibit adenylyl cyclase (Reppert SM et al, 1994: Reppert SM et al, 1995).
Platelet-activating factor (PAF, AGEPC, acetyl-glyceryl-ether-phosphorylcholine) is a potent phospholipid activator and mediator of many leukocyte functions, including platelet aggregation, inflammation, and anaphylaxis. It is an important mediator of bronchoconstriction. It causes platelets to aggregate and blood vessels to dilate so is important to the process of hemostasis. The PAF receptor (Ye RD et al, 1991) shows structural characteristics of the rhodopsin gene family and binds platelet-activating factor (PAF). The activity of this receptor is mediated by coupling with the G protein alpha q subunit which stimulates PLC-beta which can cleave PIP2 to form secondary messengers (Deo DD et al, 2004).
The LPA-binding EDG receptors all bind to the ligand lysophosphatidic acid (LPA), a phospholipid derivative that acts as a potent signaling molecule. EDG2 is a human gene encoding a GPCR, LPA1 (as this receptor binds LPA) (An S et al, 1997). Downstream effects such as inhibition of adenylyl cyclase are mediated by binding to Gi proteins (An S et al, 1998). EDG4 is a human gene which encodes the GPCR known as LPA2 (An S et al, 1998). This protein contributes towards Ca2+ mobilization, a critical cellular response to LPA in cells, through association with Gi and Gq proteins (An S et al, 1998). EDG7 encodes the GPCR LPA3. This receptor binds LPA and mediates LPA-evoked calcium mobilization. This receptor couples predominantly to Gq/11 alpha proteins (Im DS et al, 2000).
The cannabinoid receptors are a class of receptors within the G-protein coupled receptor superfamily. Their ligands are known as cannabinoids or endocannabinoids depending on whether they come from external or internal (endogenous) sources, respectively (Howlett et al. 2002). Endocannabinoids serve as intercellular lipid messengers, signaling molecules that are released from one cell and activate the cannabinoid receptors present on other cells. Cannabinoid type 1 (CB1) receptors (Gerrard et al. 1990) are thought to be the most widely expressed G-protein coupled receptors in the brain, lungs, liver and kidneys. Endocannabinoids released from the depolarized neuron bind to CB1 receptors in the pre-synaptic neuron and cause a reduction in GABA release. CB2 receptors (Munro et al. 1993) are mainly expressed on T cells of the immune system, on macrophages and B cells, and in hematopoietic cells. Current research suggests that these receptors play a role in nociception, or the perception of pain. Both receptors' activity is mediated by coupling to the G protein alpha i/o subunit, which inhibits adenylyl cyclase (Bouaboula et al. 1995, Bayewitch et al. 1995). GPR55 is activated by plant cannabinoids and the endocannabinoids 2-arachidonoyl glycerol (2-AG) and anandamide (AEA), leading to suggestions that it should be renamed CB3. However GPR55 has also been reported as a receptor for LPI and its derivative 2-Arachidonoyl-sn-glycero-3-phosphoinositol. 2-AG binds to the CB1 and CB2 receptors with similar affinity, acting as a full agonist.
Five EDG-encoded receptors can all bind sphingolipid-1-phosphate (S1P), a second messenger implicated in cell survival, cell migration, and inflammation. The five genes encoding the receptors are EDG1, 3, 5, 6 and 8. EDG1 is a human gene which encodes a GPCR which binds S1P. Hence this receptor is also known as S1PR1 (Hla T, Maciag T, 1990). S1PR1 seems to couple with Gi proteins (Lee MJ et al, 1996). EDG5 encodes the GPCR known as S1PR2 (An S et al, 2000). This protein participates in S1P-induced cell proliferation, survival, and transcriptional activation, effects mediated by coupling to Gi and Gq proteins (Windh RT et al, 1999). EDG3 encodes a GPCR known as S1PR3 (Yamaguchi F et al, 1996). This protein contributes to the regulation of angiogenesis and vascular endothelial cell function. These effects are mediated by coupling with Gi, Gq/11 and G12/13 proteins (Windh RT et al, 1999). EDG6 encodes the GPCR known as S1PR4 (Graler MH et al, 1998). This EDG receptor gene is intronless and is specifically expressed in the lymphoid tissue. It's actions are mediated by coupling with Gi/o proteins to inhibit adenylyl cyclase (Van Brocklyn JR et al, 2000). EDG8 encodes the GPCR known as S1PR5 (Kothapalli R et al, 2002). Its actions are mediated by coupling with Gi/o proteins to inhibit adenylyl cyclase (Im DS et al, 2000).
Rhodopsin (encoded by the human gene OPN2) (Nathans J and Hogness DS, 1984) is expressed in rod photoreceptor cells used in night vision. In humans, three opsins are expressed in cone cells used for colour vision. The opsin 1 gene OPN1MW encodes a protein called green cone photopigment or medium-wave-sensitive opsin (Nathans J et al, 1986). Defects in OPN1MW are the cause of partial colorblindness called deuteranopia (Winderickx J et al, 1992). The opsin 1 gene OPN1LW encodes a protein called red cone photopigment or long-wavelength sensitive opsin (Nathans J et al, 1986). Defects in this gene are the cause of partial colorblindness (protanopia) (Winderickx J et al, 1992). The opsin 1 gene OPN1SW encodes for blue-sensitive opsins (BOP) (Nathans J et al, 1986). A deficiency in function or numbers (or both) of BOP results in a selective deficiency of blue spectral sensitivity. This is called Tritanopia, an autosomal dominant genetic disorder of human vision (Weitz CJ et al, 1992). The human gene OPN3 encodes opsin 3 (encephalopsin, panopsin) (Blackshaw S and Snyder SH, 1999). It is strongly expressed in brain and testis with features of a classical photoreceptive opsin. The human gene OPN5 encodes opsin 5, which is expressed in the eye, brain, testes, and spinal cord (Tarttelin EE et al, 2003). The visual pigment-like receptor peropsin (RRH) is found only in the eye, where it is localized to the retinal pigment epithelium (RPE) (Sun H et al, 1997). In the RPE, it is localized to the microvilli that surround the photoreceptor outer segments. It may play a role in RPE physiology, either by detecting light directly or by monitoring the concentration of retinoids or other photoreceptor-derived compounds. The putative RPE-retinal G protein coupled receptor (RGR) (Shen D et al, 1994) covalently binds both all-trans- and 11-cis-retinal after reduction by sodium borohydride. The 32-kDa receptor binds all-trans-retinal preferentially, rather than the 11-cis isomer. Defects in RGR are a cause of autosomal recessive retinitis pigmentosa (ARRP). RP leads to degeneration of retinal photoreceptor cells (Morimura H et al, 1999). Transducin (also called Gt) is a heterotrimeric G protein that is naturally expressed in vertebrate retina rods and cones and couple with these opsins to mediate the stimulation of cGMP hydrolysis.
Melanopsin (Opsin-4) (Provencio I et al, 2000) is a member of the opsin family encoded by the OPN4 gene. It is found in specialized photosensitive ganglion cells of the retina that are involved in the regulation of circadian rhythms, pupillary light reflex, and other non-visual responses to light. Melanopsin is expressed only in the retina and there, only in 1-2% of the ganglion cells. The effects of melanopsin are mediated by coupling to Gq/11 proteins which results in increased intracellular calcium levels (Qiu X et al, 2005).
CCR11 binds CCL19, CCL21, and CCL25 but calcium signalling is low level, consequently it is regarded by some as a scavenger receptor (Comerford et al. 2006).
Free fatty acid receptor 3 (FFAR3/GPR41) is activated by carboxylate anion ligands with a rank order of potency: propionate = pentanoate = butyrate > acetate > formate.
GPR120 is a receptor for many unsaturated long-chain free fatty acids (FFAs) with carbon chains 16-22 in length, the most potent tested being alpha-linolenic acid. Stimulation of GPR120 signals via G-alpha- q (Hirasawa et al. 2005, Oh et al. 2010)
Free fatty acid receptor 1 (FFAR1/GPR40) is activated by many medium-length fatty acids. In recombinant assays the most potent saturated fatty acids had carbon chain lengths of 15-16; the most potent unsaturated fatty acid tested was 5,8,11-Eicosatriynoic Acid (C20).
Motilin is a 22-amino acid peptide hormone expressed throughout the gastrointestinal (GI) tract of humans and other species. It affects gastric motility by stimulating interdigestive antrum and duodenal contractions. The receptor protein is known as motilin receptor, derived from the gene MLNR (first identified as GPR38).
FPRL2 is activated by the neuroprotective peptide humanin, also an agonist of FPRL1. The peptide F2L is the only reported specific agonist of FPRL2. This is an N-terminal fragment of heme-binding protein. The mechanism of cleavage and secretion of F2L is unknown.
CXC-Chemokine receptor 5 (CXCR5) was originally called Burkitts Lymphoma receptor 1 after the source tissue. The primary ligand for this receptor is CXCL13 (B-cell attracting chemokine 1 also known as B-lymphocyte chemoattractant).
The formyl peptide receptor (FPR) is activated by small peptides derived from bacterial and mitochondrial proteins, often with a formylated N terminal methionine and usually a hydrophobic amino acid at the carboxy terminal end. Formyl-MetLeuPhe is the most commonly used peptide ligand, leading to a widespread use of the name fMetLeuPhe receptor.
Formyl peptides are produced by the degradation of either bacterial or host cells. They have a wide range of biological activities including the stimulation of chemotaxis and secretory activities of leukocytes, particularly neutrophils and monocytes. Formyl peptide receptors are involved in mediating immune cell responses to infection.
Zn2+ is a potent and effective agonist of GPR39, signaling effectively through the Gq pathway (Holst et al. 2004, 2007) and Gs (Zhang et al. 2005, Holst et al. 2007).
Neuropeptide S receptor (NPSR) is also called G protein-coupled receptor for asthma susceptibility (GPRA) and GPR154. NPSR is activated by neuropeptide S (NPS), a bioactive peptide that modulates stress and arousal.
NPSR is thought to be Gs and Gq coupled (Gupte et al. 2004).
The complement component 3a receptor (C3AR) binds C3a, a 77-amino acid anaphylatoxin generated after proteolytic cleavage of C3 and C5 in response to complement activation. C3a is involved in a variety of inflammatory responses including chemotaxis and activation of granulocytes, mast cells and macrophages (Peng et al. 200, Klos et al. 2009).
The G-protein coupled bile acid receptor (GPBAR1) responds to several bile acids the most potent being lithocholic acid. Primary bile acids are acidic sterols synthesized from cholesterol in the liver where they are conjugated with glycine or taurine. Following synthesis bile acids are stored in the gall bladder and secreted into the duodenum where they facilitate solubilization and absorption of lipid-soluble vitamins and dietary fats. Bile acids can also regulate expression of various transport proteins and enzymes through the binding and activation of nuclear receptors, particularly FXR.
Prokineticin receptors 1 and 2 are receptors for the bioactive peptides Prokineticin 1 and prokineticin 2 (PK1 and PK2). Both PKs have 10 conserved cysteines and about 40% amino acid identity with each other. PKs potently contract gastrointestinal smooth muscle.
The subfamily of G protein-coupled receptors comprising GPR4, OGR1, TDAG8, and G2A was originally characterized as a group of proteins mediating biological responses to the lipid messengers sphingosylphosphorylcholine (SPC), lysophosphatidylcholine (LPC), and psychosine. This was later replaced by reports that OGR1 and GPR4 sense acidic pH. GPR4, OGR1, and TDAG8 are now considered as proton-sensing receptors.
Relaxin-3 receptor 2 (RXFP4 or GPR100) is activated by relaxin-3 and by INSL5. Because of overlapping expression patterns between ligand and receptor Relaxin-3 receptor 2 is considered to be a high affinity INSL5 receptor.
Relaxin receptor 2 (RXFP2 or LGR8) is activated by porcine relaxin, human relaxin-2 and insulin-like peptide-3 (INSL3). Relaxin affinity is lower than for Relaxin receptor 1, suggesting that this receptor functions as an INSL3 receptor.
Urotensin-II (U2) is a vasoactive 'somatostatin-like' cyclic peptide originally isolated from fish spinal cords. It was found to activate GPR14 later renamed Urotensin II receptor (U2R).
U2 is the most potent known vasoconstrictor. A second ligand for U2R, urotensin-related peptide or Urotensin 2B, was identified as an extract from rat brains, and shown to activate rat and human U2R.
GPR37 and GPR37L1 are almost exclusively expressed in the nervous system. They bind and are activated by the secreted neuroprotective and glioprotective factor prosaposin and a fragment of this named prosaptide. Signaling involves G-alpha-i/o.
GPR37L1 and GPR73 are almost exclusively expressed in the nervous system. They bind and are activated by the secreted neuroprotective and glioprotective factor prosaposin and a fragment of this named prosaptide.
The Kell blood group glycoprotein (KEL) is a zinc endopeptidase with endothelin-3-converting enzyme activity which can preferentially cleave endothelin-3 (EDN3), an endothelium-derived vasoconstrictor peptide. EDN3 is cleaved at Trp21-Ile22 to form the bioactive peptide EDN3(97-117) (Lee et al. 1999). KEL forms a heterodimer with membrane transport protein XK (Russo et al. 1998).
Human plasticity-related genes (PRGs, lipid phosphate phosphatase-related proteins LPPRs) comprise 5 members expressed in the CNS. They are membrane-spanning enzymes thought to mediate the extracellular concentration and signal transduction of lipid phosphate esters such as lysophosphatidic acid (LPA) and spingosine-1 phosphate (S1P) by hydrolysing their phosphate groups. LPPR4 has been shown to act as an ecto-enzyme in axon growth and regenerative sprouting by mediating LPA levels (Brauer et al. 2003). The activity of the other LPPR members has yet to be defined (Strauss & Brauer 2013).
GPR35 is expressed both in neurons and other cells (including glia, macrophages and monocytes). KYNA has been proposed as the endogenous agonist of GPR35 (Wang et al. 2006).
Kynurenic acid (KYNA) is a tryptophan metabolite (Moroni 1999). It can selectively antagonize NMDA type glutamate receptors (Perkins & Stone 1982).
GPR143, also known as Ocular albinism 1 (OA1) binds L-dopamine (L-Dopa) (Lopez et al. 2008, Hiroshima et al. 2014), the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) collectively known as catecholamines. L-Dopa is in intermediate of melanin biosynthesis (Aroca et al. 1993, Roffler-Tarlov et al. 2013). GPR143 is present on the apical cell surface of retinal pigment epithelial cells (Lopez et al. 2008).
GPR143 can associate with several Galpha subunits, Gbeta and arrestin (Schiaffino & Tacchetti 2005, Innamorati et al. 2006). Its signalling is pertussis toxin sensitive and therefore likely to be mediated by Gq (Lopez et al. 2008).
CCR8 is the receptor for CCL1 (Roos et al. 1997, Tiffany et al. 1997)Goya et al. 1998, Dairaghi et al. 1999). CCL1-induced mobilization of intracellular calcium was inhibited by pertussis toxin, suggesting that CCR8 is coupled to the Gi class of Galpha subunits (Tiffany et al. 1997, Goya et al. 1998)
GPR183 (Epstein-Barr virus-induced gene 2, EBI2) is a G protein-coupled receptor that is expressed in peripheral blood mononuclear cells and the CNS. It is activated by the oxysterol 7-alpha-25-dihydroxycholesterol (7A25HC) (Hannedouche et al. 2011). EBI2 is coupled exclusively to Gi (Rosenkilde et al. 2006).
Chemokine-like receptor 1 (CMKLR1, ERV1, CHEMR23, DEZ) is activated by the essentil fatty acid-derived, pro-inflammation resolving ligand resolvin E1 (RvE1), which is the result of sequential enzymatic conversion of the omega-3 fatty acid eicosapentaenoic acid (EPA) by aspirin-modified cyclooxygenase or cytochrome P450 and 5-lipoxygenase. RvE1 is produced in both 18(S)- and 18(R)-stereoisomeric forms (Arita et al. 2005, 2007).
CMKLR1 is also reported to be a receptor for chemerin (Wittamer et al. 2003) and RvE1 is reported to be a partial agonist for Leukotriene B4 receptor 1 (LTB4R, BLT1, CMKRL1) (Arita et al. 2007).
CMKLR1 signals via the Akt/rS6/mTOR pathway (Ohira et al. 2010). This RvE1 mediated signaling influences is believed to actively promote the resolution of inflammation (Freire et al. 2017).
C-C motif chemokine 13 (MCP-4, CCL13) is a chemotactic factor that attracts monocytes, lymphocytes, basophils and eosinophils, but not neutrophils. It signals through the CCR2B and CCR3 receptors.
Endothelin-converting enzyme 1 (ECE1) is a type II membrane-bound zinc metalloprotease. It cleaves the longer form of endothelin (EDN1(53-90), also known as Big ET-1, by an unusual selective hydrolysis of Trp21-Val22, producing EDN1. ECE1 exhibits maximal activity at pH 7.0. It comprises a short cytoplasmic N-terminal tail, a membrane-spanning region, and a large extracellular domain containing a zinc-binding motif essential for enzymatic activity (Schweizer et al. 1997, Valdenaire et al.1999, Jeng et al. 2002).
Endothelin-converting enzyme 2 (ECE2) belongs to the type II membrane-bound zinc metalloprotease family and shares 59% sequence similarity to ECE1 (Emoto & Yanagisawa1995, Yanagisawa et al. 2000, Lorenzo et al. 2001). In contrast to ECE1, the optimum pH for ECE2 activity is acidic (pH 5.5), which would favor an intracellular localization and a potential role under low pH conditions, for example in ischemia. This difference provides an experimental method for distinguishing between the activities of the two enzymes. ECE2 was found to be localized to the acidified environment of vesicles of the secretory pathway in human endothelial cells but was not detected in Weibel-Palade storage granules (Russell & Davenport 1999).
Neurolysin (NLN, EC 3.4.24.16) is a member of the thermolysin-like mammalian zinc endopeptidase family (Dauch et al. 1995). It is maximally active at neutral pH and responsible for hydrolytic processing of bioactive peptides in the extracellular environment (Shrimpton et al. 2002). It cleaves 3 residues from the C-teminal end of Neurotensin (Dauch et al. 1995).
Other endogenous substrates of NLN include bradykinin, angiotensins I and II, substance P, hemopressin, dynorphin A(1–8), metorphamide, and somatostatin (Wangler et al. 2016). The functional significance of NLN is poorly understood (Checler 2014). In vivo studies have linked it to neurotensin-dependent nociception (Vincent et al. 1997), bradykinin-mediated hypotension, microvascular permeability and hyperalgesia (Gomez et al. 2011), and pathogenesis of stroke (Rashid et al. 2014).
Ghrelin is a 27 or 28 residue long peptide that is the ligand of Growth hormone secretagogue receptor type 1 (GHSR). O-octanoylation or O-decanoylation is essential for ghrelin activity. GHSR activation induces the release of growth hormone from the pituitary. It has an appetite-stimulating effect, induces adiposity and stimulates gastric acid secretion. Involved in growth regulation.
Two Melanin-concentrating hormone receptors have been characterized in humans. Many non-human species (rat, mouse, hamster, guinea pig and rabbit) do not have a functional MCHR2 receptor, or encode a nonfunctional MCHR2 pseudogene (Tan et al. 2002). The receptors bind melanin concentrating hormone, a cyclic peptide predominantly expressed in the hypothalamus that functions as a neurotransmitter controlling a range of functions. A major role of MCH is thought to be in the regulation of feeding: injection of MCH into rat brains stimulates feeding; expression of MCH is upregulated in the hypothalamus of obese and fasting mice; and mice lacking MCH are lean and eat less. MCH and alpha melanocyte-stimulating hormone (alpha-MSH) have antagonistic effects on a number of physiological functions. Alpha-MSH darkens pigmentation in fish and reduces feeding in mammals, whereas MCH increases feeding.
The neuromedin-U receptors bind the neuropeptides neuromedin-U and neuromedin-S. Neuromedin U is an agonist at both the NMUR1 and NMUR2 subtypes, while neuromedin S is selective for NMUR2, and is a more potent agonist for NMUR2 than neuromedin-U.
C5AR2 (GPR77, C5L2) has been described as a receptor for the chemotactic and inflammatory peptides anaphylatoxin C5a, C4a and C3a and even their des-arginated derivatives. Highest binding affinity was for C3a-desArg, also called Acylation Stimulating Protein (ASP), produced from C3a following arginine removal by carboxypeptidases. Binding of C3a and its derivatives has been disputed (Johswich et al. 2006) leading to suggestions that this receptor may be a C5a scavenger. It is weakly coupled to G(i)-mediated signaling pathways and believed to function primarily as a decoy receptor though it can interact with beta arrestin (Van Lith et al. 2009).
Neuromedin-U receptor 2 binds the neuromedin-U and neuromedin-S. While neuromedin-U is an agonist at both the NMUR1 and NMUR2 subtypes, neuromedin-S is selective for NMUR2, and a more potent agonist for NMUR2 than neuromedin-U.
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CMKLR1 is also reported to be a receptor for chemerin (Wittamer et al. 2003) and RvE1 is reported to be a partial agonist for Leukotriene B4 receptor 1 (LTB4R, BLT1, CMKRL1) (Arita et al. 2007).
CMKLR1 signals via the Akt/rS6/mTOR pathway (Ohira et al. 2010). This RvE1 mediated signaling influences is believed to actively promote the resolution of inflammation (Freire et al. 2017).
CMKLR1 is also reported to be a receptor for chemerin (Wittamer et al. 2003) and RvE1 is reported to be a partial agonist for Leukotriene B4 receptor 1 (LTB4R, BLT1, CMKRL1) (Arita et al. 2007).
CMKLR1 signals via the Akt/rS6/mTOR pathway (Ohira et al. 2010). This RvE1 mediated signaling influences is believed to actively promote the resolution of inflammation (Freire et al. 2017).
receptors:NPY
receptor ligandsB/W
receptor:neuropeptides B/Wreceptor:opioid
ligandamine-associated
receptor:PEAamine-associated
receptorAnnotated Interactions
receptors:NPY
receptor ligandsB/W
receptor:neuropeptides B/Wreceptor:opioid
ligandCXCL1 (previously known as GRO1 oncogene; NAP-3; MSGA-alpha) (Richmond A et al, 1988) is expressed by neutrophils, macrophages and epithelial cells and possesses neutrophil chemoattractant activity. It is secreted by melanoma cells and is implicated in melanoma pathogenesis. CXCL2 (MIP2-alpha;Gro-beta;Gro-2) (Iida N and Grotendorst GR, 1990; Haskill S et al, 1990) is closely related to CXCL1 (90% amino acid sequence). It is secreted by monocytes and macrophages and attracts polymorphonuclear leukocytes and hematopoietic stem cells. CXCL3 (GRO3; GROg; MIP2-beta) (Haskill S et al, 1990) controls the migration and adhesion of monocytes.
CXCL4 (platelet factor 4, PF4) (Poncz M et al, 1987) is released from platelets during aggregation and promotes blood coagulation by neutralization of heparin-like molecules. It is chemotactic for neutrophils, fibroblasts and monocytes. Due to all these roles, CXCL4 is implicated in wound repair and inflammation. CXCL5 (ENA-78) (Walz A et al, 1991) is produced by cells which have been stimulated by interleulin-1 or tumor necrosis factor-alpha. CXCL7 (pro-platelet basic protein, PPBP) (Holt JC et al, 1986) is released from platelets once they are activated. It can stimulate various processes including glucose metabolism, mitogenesis and syntheses of plasminogen activator and extracellular matrix.
The enkephalins are endogenous ligands, or specifically endorphins, as they are internally derived and bind to the body's opioid receptors. There are two forms of enkephalin, one containing leucine ("leu"), while the other contains methionine ("met"). The met-enkephalin peptide sequence is coded by the POMC gene whereas leu-enkephalin is coded by both POMC and dynorphin genes. Enkephalins are pentapeptides involved in regulating pain and nociception in the body. Their action is mediated through the delta-opioid receptor (DOR) (Knapp RJ et al, 1994).
Dynorphins constitute a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released, amongst which are dynorphin A, dynorphin B, big-dyn and alpha/beta-neoendorphin (Day R et al, 1998). Dynorphins primarily exert their effects through the kappa-opioid receptor (KOR), a G-protein coupled receptor (Simonin F et al, 1995). Two subtypes of KORs have been identified: K1 and K2. Although KOR is the primary receptor for all dynorphins (James IF et al, 1982), the peptides do have some affinity for MOR and DOR.
These bind to two receptors, designated ETA (Adachi M et al, 1991) and ETB (Nakamuta M et al, 1991). ETA receptors are primarily located in smooth muscle of blood vessels. Endothelin binding to ETA causes vasoconstriction and sodium retention, leading to increased blood pressure. ETB are primarily located on endothelial cells lining the internal walls of vasculature. Endothelin binding to ETB leads to the release of NO (nitric oxide) which is a strong vasodilator.
Neuropeptide Y peptides are also implicated as mediators in the pathogenesis of many gastrointestinal disorders, including malabsorption, short gut, inflammatory bowel diseases, and forms of pancreatitis. The three peptides are neuropeptide Y (NPY) (Minth CD et al, 1984), peptide YY (PYY) (Tatemoto K et al, 1988) and pancreatic peptide (PP) (Boel E et al, 1984).
Although each peptide can bind to any of the four receptors, they each have preferred receptors. NPY binds preferentially to NPY1R, PYY to NYP2R and PP to NYP4R.
All of these three receptors couple with Gq/11 protein which use the upregulation of phospholipase C and therefore inositol trisphosphate and intracellular calcium as a signaling mechanism (Bräuner-Osborne H and Brann MR, 1996).
Histamine H4 receptor (Nakamura T et al, 2000) is highly expressed in bone marrow and white blood cells. It is also found in other tissues such as colon, liver, lungs and thymus. The H4 receptor mediates mast cell chemotaxis. Both the H3 and H4 receptors mediate their actions by coupling with the G protein alpha-i subtype, thus decreasing intracellular cAMP.
All these receptor types mediate their actions by coupling to the G protein alpha-s subtype, which increases cellular cAMP levels (Baker LP et al, 1998; Zhang JY et al, 2003).
Thyrostimulin is a dimer of Glycoprotein hormone alpha-2 (GPHA2) and Glycoprotein hormone beta-5(GPHB5), comprising the a fifth glycoprotein hormone (Nakabayashi et al. 2002), a more potent ligand for the TSH receptor than TSH which has a wider tissue distribution (Huang et al. 2016).
These effects are mediated by the TSH receptor (Nagayama Y et al, 1989), found primarily on thyroid follicular cells. The activated receptor couples with the G protein alpha-s subunit (Allgeier A et al 1994) which activates adeylate cyclase and increases intracellular cAMP levels.Once activated, the receptor mediates its action by coupling to the G protein alpha-s subunit (Timossi C et al, 2002), which activates adenylate cyclase and increases intracellular cAMP levels.
The A3 receptor (Salvatore CA et al, 1993) mediates a sustained cardioprotective function during cardiac ischemia and it is involved in the inhibition of neutrophil degranulation in neutrophil-mediated tissue injury.
Both the A1 and A3 receptors mediate their effects by coupling with the G protein alpha i subunit which inhibits adenylyl cyclase (Wise A et al, 1999).
Both ADORA receptors mediate their actions by coupling with the G protein alpha s subunit which activates adenylyl cyclase and increases intracellular cAMP concentrations. In surfactant physiology, the receptor:adenosine complex positively regulates surfactant export from lamellar bodies. (Cooper JA et al, 1995; Linden J et al, 1999). Adenosine deaminase (CECR1, ADA2) degrades extracellular adenosine (Ade-Rib), reducing or neutralising the positive regulatory effect of adenosine in surfactant export.
EDG2 is a human gene encoding a GPCR, LPA1 (as this receptor binds LPA) (An S et al, 1997). Downstream effects such as inhibition of adenylyl cyclase are mediated by binding to Gi proteins (An S et al, 1998).
EDG4 is a human gene which encodes the GPCR known as LPA2 (An S et al, 1998). This protein contributes towards Ca2+ mobilization, a critical cellular response to LPA in cells, through association with Gi and Gq proteins (An S et al, 1998).
EDG7 encodes the GPCR LPA3. This receptor binds LPA and mediates LPA-evoked calcium mobilization. This receptor couples predominantly to Gq/11 alpha proteins (Im DS et al, 2000).
Cannabinoid type 1 (CB1) receptors (Gerrard et al. 1990) are thought to be the most widely expressed G-protein coupled receptors in the brain, lungs, liver and kidneys. Endocannabinoids released from the depolarized neuron bind to CB1 receptors in the pre-synaptic neuron and cause a reduction in GABA release.
CB2 receptors (Munro et al. 1993) are mainly expressed on T cells of the immune system, on macrophages and B cells, and in hematopoietic cells. Current research suggests that these receptors play a role in nociception, or the perception of pain.
Both receptors' activity is mediated by coupling to the G protein alpha i/o subunit, which inhibits adenylyl cyclase (Bouaboula et al. 1995, Bayewitch et al. 1995).
GPR55 is activated by plant cannabinoids and the endocannabinoids 2-arachidonoyl glycerol (2-AG) and anandamide (AEA), leading to suggestions that it should be renamed CB3. However GPR55 has also been reported as a receptor for LPI and its derivative 2-Arachidonoyl-sn-glycero-3-phosphoinositol. 2-AG binds to the CB1 and CB2 receptors with similar affinity, acting as a full agonist.
EDG1 is a human gene which encodes a GPCR which binds S1P. Hence this receptor is also known as S1PR1 (Hla T, Maciag T, 1990). S1PR1 seems to couple with Gi proteins (Lee MJ et al, 1996).
EDG5 encodes the GPCR known as S1PR2 (An S et al, 2000). This protein participates in S1P-induced cell proliferation, survival, and transcriptional activation, effects mediated by coupling to Gi and Gq proteins (Windh RT et al, 1999).
EDG3 encodes a GPCR known as S1PR3 (Yamaguchi F et al, 1996). This protein contributes to the regulation of angiogenesis and vascular endothelial cell function. These effects are mediated by coupling with Gi, Gq/11 and G12/13 proteins (Windh RT et al, 1999).
EDG6 encodes the GPCR known as S1PR4 (Graler MH et al, 1998). This EDG receptor gene is intronless and is specifically expressed in the lymphoid tissue. It's actions are mediated by coupling with Gi/o proteins to inhibit adenylyl cyclase (Van Brocklyn JR et al, 2000).
EDG8 encodes the GPCR known as S1PR5 (Kothapalli R et al, 2002). Its actions are mediated by coupling with Gi/o proteins to inhibit adenylyl cyclase (Im DS et al, 2000).
The opsin 1 gene OPN1LW encodes a protein called red cone photopigment or long-wavelength sensitive opsin (Nathans J et al, 1986). Defects in this gene are the cause of partial colorblindness (protanopia) (Winderickx J et al, 1992). The opsin 1 gene OPN1SW encodes for blue-sensitive opsins (BOP) (Nathans J et al, 1986). A deficiency in function or numbers (or both) of BOP results in a selective deficiency of blue spectral sensitivity. This is called Tritanopia, an autosomal dominant genetic disorder of human vision (Weitz CJ et al, 1992).
The human gene OPN3 encodes opsin 3 (encephalopsin, panopsin) (Blackshaw S and Snyder SH, 1999). It is strongly expressed in brain and testis with features of a classical photoreceptive opsin. The human gene OPN5 encodes opsin 5, which is expressed in the eye, brain, testes, and spinal cord (Tarttelin EE et al, 2003).
The visual pigment-like receptor peropsin (RRH) is found only in the eye, where it is localized to the retinal pigment epithelium (RPE) (Sun H et al, 1997). In the RPE, it is localized to the microvilli that surround the photoreceptor outer segments. It may play a role in RPE physiology, either by detecting light directly or by monitoring the concentration of retinoids or other photoreceptor-derived compounds.
The putative RPE-retinal G protein coupled receptor (RGR) (Shen D et al, 1994) covalently binds both all-trans- and 11-cis-retinal after reduction by sodium borohydride. The 32-kDa receptor binds all-trans-retinal preferentially, rather than the 11-cis isomer. Defects in RGR are a cause of autosomal recessive retinitis pigmentosa (ARRP). RP leads to degeneration of retinal photoreceptor cells (Morimura H et al, 1999).
Transducin (also called Gt) is a heterotrimeric G protein that is naturally expressed in vertebrate retina rods and cones and couple with these opsins to mediate the stimulation of cGMP hydrolysis.
Formyl peptides are produced by the degradation of either bacterial or host cells. They have a wide range of biological activities including the stimulation of chemotaxis and secretory activities of leukocytes, particularly neutrophils and monocytes. Formyl peptide receptors are involved in mediating immune cell responses to infection.
U2 is the most potent known vasoconstrictor. A second ligand for U2R, urotensin-related peptide or Urotensin 2B, was identified as an extract from rat brains, and shown to activate rat and human U2R.Kynurenic acid (KYNA) is a tryptophan metabolite (Moroni 1999). It can selectively antagonize NMDA type glutamate receptors (Perkins & Stone 1982).
CMKLR1 is also reported to be a receptor for chemerin (Wittamer et al. 2003) and RvE1 is reported to be a partial agonist for Leukotriene B4 receptor 1 (LTB4R, BLT1, CMKRL1) (Arita et al. 2007).
CMKLR1 signals via the Akt/rS6/mTOR pathway (Ohira et al. 2010). This RvE1 mediated signaling influences is believed to actively promote the resolution of inflammation (Freire et al. 2017).
amine-associated
receptor:PEAamine-associated
receptor