Cannabinoid receptor signaling (Homo sapiens)

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5CYP3A4CYP2C196CBD catabolismPKARelevant MAPK subtypesendogenous cannabinoidsNeuronal cell of CNS(hyppocampus, cerebellum or basal ganglia)inactiveInhibition of Glutamate or GABA release in synaptic cleftLeukocytes, spleen, thymus, bone marrowand other tissues associated with immune functionsHepG2 cellsPRKACBMAPK13PRKAR1BMAPK14MAPK9MAPK12MAPK10MAPK8PRKACAMAPK1PRKAR1APRKAR2BMAPK3ADCY1PRKACGMAPK11PRKAR2ACNR1CYP2C911-OH-THCMAPK PhosphatidylethanolamineDAGLBcAMP AHRNAPEPLD1ADCY77NAPEDAGLA1Arachidonic acidTHC1''-hydroxycannabidiol62-arachidonoylglycerolprotein tyrosine kinasesFAAH1GlutamateADORA2A4CNR2CalciumGABA CBDATPAEAAnti-inflammatory pathwaysCOOH-THC2CYP1A13ATPcAMP CBD2''-hydroxycannabidiol 63''-hydroxycannabidiol 64''-hydroxycannabidiol 65''-hydroxycannabidiol 66a-hydroxycannabidiol 66b-hydroxycannabidiol 67-hydroxycannabidiol endogeneous cannabinoid synthesis6PRKACBPRKACAPRKAR1APRKAR2BPRKAR1BPRKACGPRKAR2APKA regulatory subunit type IPKAcatalytic subunitPKA regulatory subunit type IIPRKACBPRKACAPRKAR1APRKAR2BPRKAR1BPRKACGPRKAR2APKA


Description

Endogenous cannabinoid receptors belong to the endocannabinoid system and are located in the mammalian brain and throughout the central and peripheral nervous systems, consisting of neuromodulatory lipids and their receptors. The endocannabinoid system is involved in a variety of physiological processes including appetite, pain-sensation, mood, and memory, and in mediating the psychoactive effects of cannabis. Two primary endocannabinoid receptors have been identified: CNR1 and CNR2. CNR1 is found predominantly in the brain and nervous system, as well as in peripheral organs and tissues, and are the main molecular target of the endocannabinoid ligand (binding molecule), Anandamide, as well as its mimetic phytocannabinoid, THC (tetrahydrocannabinol). One other main endocannabinoid is 2-Arachidonoylglycerol (2-AG) which is active at both cannabinoid receptors, along with its own mimetic phytocannabinoid, CBD (cannabidiol). 2-AG and CBD are involved in the regulation of appetite, immune system functions and pain management.

Source: https://en.wikipedia.org/wiki/Endocannabinoid_system

Not all MAPK subtypes are relevant for this pathway. The relevant types have been separately added on the right side of the pathway.

Source: Howlett A.C. Cannabinoid Receptor Signaling. In: Pertwee R.G. (eds) Cannabinoids. Handbook of Experimental Pharmacology, vol 168. Springer, Berlin, Heidelberg, 2005

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Bibliography

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  1. Díaz-Alonso J, Guzmán M, Galve-Roperh I; ''Endocannabinoids via CB� receptors act as neurogenic niche cues during cortical development.''; Philos Trans R Soc Lond B Biol Sci, 2012 PubMed Europe PMC Scholia
  2. Anderson GD, Chan LN; ''Pharmacokinetic Drug Interactions with Tobacco, Cannabinoids and Smoking Cessation Products.''; Clin Pharmacokinet, 2016 PubMed Europe PMC Scholia
  3. Yamaori S, Kinugasa Y, Jiang R, Takeda S, Yamamoto I, Watanabe K; ''Cannabidiol induces expression of human cytochrome P450 1A1 that is possibly mediated through aryl hydrocarbon receptor signaling in HepG2 cells.''; Life Sci, 2015 PubMed Europe PMC Scholia
  4. Carrier EJ, Auchampach JA, Hillard CJ; ''Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression.''; Proc Natl Acad Sci U S A, 2006 PubMed Europe PMC Scholia
  5. Laprairie RB, Bagher AM, Kelly ME, Denovan-Wright EM; ''Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor.''; Br J Pharmacol, 2015 PubMed Europe PMC Scholia
  6. Jiang R, Yamaori S, Takeda S, Yamamoto I, Watanabe K; ''Identification of cytochrome P450 enzymes responsible for metabolism of cannabidiol by human liver microsomes.''; Life Sci, 2011 PubMed Europe PMC Scholia
  7. ; ''''; http://www.genecards.org/cgi-bin/carddisp.pl?gene=CNR2&keywords=cnr2,

History

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CompareRevisionActionTimeUserComment
118463view15:04, 27 May 2021FinterlyMoved URL to Source for rdf:id b2b
106148view12:04, 16 August 2019MaintBotHMDB identifier normalization
98007view07:54, 3 July 2018Fehrhartfixed aesthetics
97566view07:39, 25 May 2018IreneHemelModified description
97565view07:39, 25 May 2018IreneHemelModified description
97564view07:36, 25 May 2018IreneHemelAddition of relevant MAPK subtypes
97536view14:31, 24 May 2018IreneHemelSubunits PKA
94926view11:40, 13 October 2017DeSlOntology Term : 'xenobiotic metabolic pathway' added !
94925view11:38, 13 October 2017DeSladded ID for 2nd PKA node
94924view11:37, 13 October 2017DeSladded ID for PKA
94923view11:36, 13 October 2017DeSladded ID for MAPK
88989view11:44, 18 August 2016Mkutmonremoved comments
88980view09:30, 18 August 2016Fehrhartfixed some weird characters
88978view09:18, 18 August 2016Fehrhartadjusted some lines and added descriptions
88975view09:12, 18 August 2016Fehrhartaddition of OH-CBDs
88973view08:36, 18 August 2016FehrhartModified description
88834view13:13, 15 August 2016Fehrhartwork in progress
88833view13:10, 15 August 2016FehrhartModified description
88598view19:51, 11 August 2016Mkutmonfix unconnected lines
88457view14:38, 9 August 2016Fehrhartwork in progress
88450view15:07, 8 August 2016Fehrhartwork in progress
88449view15:02, 8 August 2016Fehrhartadded CYP1A1 stimulation pathway
88389view13:24, 3 August 2016FehrhartOntology Term : 'leukocyte' added !
88388view13:24, 3 August 2016FehrhartOntology Term : 'neuron' added !
88387view13:23, 3 August 2016FehrhartOntology Term : 'cannabinoid signaling pathway' added !
88386view13:22, 3 August 2016FehrhartWork in progress
88383view12:53, 3 August 2016FehrhartNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
1''-hydroxycannabidiolMetaboliteCHEBI:133056 (ChEBI)
11-OH-THCMetaboliteHMDB0060906 (HMDB)
2''-hydroxycannabidiol MetaboliteCHEBI:133058 (ChEBI)
2-arachidonoylglycerolMetaboliteHMDB0004666 (HMDB)
3''-hydroxycannabidiol MetaboliteCHEBI:133059 (ChEBI)
4''-hydroxycannabidiol MetaboliteCHEBI:133055 (ChEBI)
5''-hydroxycannabidiol MetaboliteCHEBI:133062 (ChEBI)
6a-hydroxycannabidiol MetaboliteCHEBI:133049 (ChEBI)
6b-hydroxycannabidiol MetaboliteCHEBI:133052 (ChEBI)
7-hydroxycannabidiol MetaboliteCHEBI:133053 (ChEBI)
ADCY1GeneProductENSG00000164742 (Ensembl)
ADCY7GeneProductENSG00000121281 (Ensembl)
ADORA2AGeneProductENSG00000128271 (Ensembl)
AEAMetaboliteHMDB0004080 (HMDB)
AHRGeneProductENSG00000106546 (Ensembl)
ATPMetaboliteHMDB0000538 (HMDB)
Anti-inflammatory pathwaysPathway
Arachidonic acidMetaboliteHMDB0001043 (HMDB)
CBDMetaboliteCHEBI:69478 (ChEBI)
CNR1GeneProductENSG00000118432 (Ensembl)
CNR2GeneProductENSG00000188822 (Ensembl)
COOH-THCMetaboliteCHEBI:77273 (ChEBI)
CYP1A1GeneProductENSG00000140465 (Ensembl)
CYP2C19GeneProductENSG00000165841 (Ensembl)
CYP2C9GeneProductENSG00000138109 (Ensembl)
CYP3A4GeneProductENSG00000160868 (Ensembl)
CalciumMetaboliteHMDB0000464 (HMDB)
DAGLAGeneProductENSG00000134780 (Ensembl)
DAGLBGeneProductENSG00000164535 (Ensembl)
FAAHGeneProductENSG00000117480 (Ensembl)
GABA MetaboliteHMDB0000112 (HMDB)
GlutamateMetaboliteHMDB0000148 (HMDB)
MAPK GeneProduct2.7.11.24 (Enzyme Nomenclature)
MAPK10GeneProductP53779 (Uniprot-TrEMBL)
MAPK11GeneProductQ15759 (Uniprot-TrEMBL)
MAPK12GeneProductP53778 (Uniprot-TrEMBL)
MAPK13GeneProductO15264 (Uniprot-TrEMBL)
MAPK14GeneProductQ16539 (Uniprot-TrEMBL)
MAPK1GeneProductP28482 (Uniprot-TrEMBL)
MAPK3GeneProductP27361 (Uniprot-TrEMBL)
MAPK8GeneProductP45983 (Uniprot-TrEMBL)
MAPK9GeneProductP45984 (Uniprot-TrEMBL)
NAPEMetaboliteCHEBI:61232 (ChEBI)
NAPEPLDGeneProductENSG00000161048 (Ensembl)
PRKACAGeneProductENSG00000072062 (Ensembl)
PRKACBGeneProductENSG00000142875 (Ensembl)
PRKACGGeneProductENSG00000165059 (Ensembl)
PRKAR1AGeneProductENSG00000108946 (Ensembl)
PRKAR1BGeneProductENSG00000188191 (Ensembl)
PRKAR2AGeneProductENSG00000114302 (EMBL)
PRKAR2BGeneProductENSG00000005249 (Ensembl)
PhosphatidylethanolamineMetaboliteHMDB0060501 (HMDB)
THCMetaboliteHMDB0041865 (HMDB)
cAMP MetaboliteHMDB0000058 (HMDB)
protein tyrosine kinasesPathway

Annotated Interactions

No annotated interactions

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