Caffeine in blood vessels (Homo sapiens)

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Description

In vascular smooth muscle, caffeine promotes relaxation by inhibiting myosin light-chain kinase (MLCK) through cAMP elevation and activating myosin light-chain phosphatase (MLCP), reducing myosin–actin interaction. As a nonselective adenosine receptor antagonist, caffeine blocks A₁/A₃ receptors (which normally lower cAMP) and A₂A/A₂B receptors (which normally raise cAMP), thereby altering adenylate cyclase activity. In endothelial cells, caffeine increases intracellular Ca²⁺, activating eNOS to produce nitric oxide (NO), which diffuses to smooth muscle and stimulates cGMP signaling, further promoting vasodilation. Inspired by [Figure 1 in Kumar and Lipshultz, 2019](https://pmc.ncbi.nlm.nih.gov/articles/PMC6915633).

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Quality Tags

Ontology Terms

 

Bibliography

  1. Kumar VHS, Lipshultz SE; ''Caffeine and Clinical Outcomes in Premature Neonates.''; Children (Basel), 2019 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
142316view12:30, 1 January 2026EgonwSmall typo fix
141489view00:34, 16 November 2025EweitzAdd identifier
141488view00:28, 16 November 2025EweitzFix "Identifier used of a amino acid with undefined stereochemistry"
141487view00:27, 16 November 2025EweitzFix "Possible MIM translocation"
141486view00:19, 16 November 2025EweitzAdd data type
141405view02:03, 12 November 2025EweitzReverted to version '13:06, 9 November 2025' by Eweitz
141404view01:57, 12 November 2025EweitzUpdate interaction to mim-translocation
141403view01:55, 12 November 2025EweitzUpdate interaction
141318view13:06, 9 November 2025EweitzAdd literature reference
141240view04:00, 7 November 2025EweitzRefine graphics
141239view03:55, 7 November 2025EweitzAdd pathway series navigation
141215view23:05, 6 November 2025EweitzOntology Term : 'caffeine metabolic pathway' added !
141214view23:05, 6 November 2025EweitzOntology Term : 'caffeine drug pathway' added !
141213view23:05, 6 November 2025EweitzOntology Term : 'endothelial cell' added !
141212view23:04, 6 November 2025EweitzModified description
141211view23:02, 6 November 2025EweitzModified description
141210view22:55, 6 November 2025EweitzAdd identifier for vasodilation
141187view12:27, 6 November 2025EweitzRefine graphics
141186view12:26, 6 November 2025EweitzRefine ER graphics
141185view12:25, 6 November 2025EweitzAdd gene identifiers
141184view12:04, 6 November 2025EweitzBolden caffeine
141183view11:57, 6 November 2025EweitzRefine interactions, economize layout
141182view11:30, 6 November 2025EweitzAdd ryanodine receptors, move sGC, refine interactions
141175view01:52, 6 November 2025EweitzEnlarge outcome
141174view01:52, 6 November 2025EweitzAdd calmodulin
141173view01:35, 6 November 2025EweitzConnect endothelial cell pathway to vasodilation
141172view01:12, 6 November 2025EweitzAdd placeholder nodes
141171view01:04, 6 November 2025EweitzAdd endothelial cell and related nodes
141166view12:19, 5 November 2025EweitzAdd phosphodiesterases
141165view11:47, 5 November 2025EweitzOntology Term : 'vascular associated smooth muscle cell' added !
141164view11:46, 5 November 2025EweitzRefine cell type, add pathway node
141163view11:41, 5 November 2025EweitzAdd MYLK, MLCP
141162view01:03, 5 November 2025EweitzAdd interactions, metabolites
141161view00:19, 5 November 2025EweitzAdd caffeine
141160view00:10, 5 November 2025EweitzAdd adenosine
141159view00:02, 5 November 2025EweitzAdd more adenosine receptors
141144view12:02, 4 November 2025EweitzAdd adenylate cyclase
141143view11:59, 4 November 2025EweitzNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADCY1GeneProductENSG00000164742 (Ensembl)
ADCY2GeneProductENSG00000078295 (Ensembl)
ADCY3GeneProductENSG00000138031 (Ensembl)
ADCY4GeneProductENSG00000129467 (Ensembl)
ADCY5GeneProductENSG00000173175 (Ensembl)
ADCY6GeneProductENSG00000174233 (Ensembl)
ADCY7GeneProductENSG00000121281 (Ensembl)
ADCY8GeneProductENSG00000155897 (Ensembl)
ADCY9GeneProductENSG00000162104 (Ensembl)
ADORA2AGeneProductENSG00000128271 (Ensembl) "A3" in source
ADORA2BGeneProductENSG00000170425 (Ensembl) "A3" in source
ADORA3GeneProductENSG00000282608 (Ensembl) "A3" in source
ADRA1AGeneProductENSG00000120907 (Ensembl) "A1" in source
ADRA1BGeneProductENSG00000170214 (Ensembl) "A1" in source
ADRA1DGeneProductENSG00000171873 (Ensembl) "A1" in source
AMPMetaboliteCHEBI:16027 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
AdenosineMetaboliteCHEBI:16335 (ChEBI)
ArginineMetaboliteCHEBI:16467 (ChEBI)
Blood vesselsPathwayWP5601 (WikiPathways)
CALM1GeneProductENSG00000198668 (Ensembl) "Calmodulin" in source
CALM2GeneProductENSG00000143933 (Ensembl) "Calmodulin" in source
CALM3GeneProductENSG00000160014 (Ensembl) "Calmodulin" in source
CaffeineMetaboliteCHEBI:27732 (ChEBI)
Ca²⁺MetaboliteCHEBI:29108 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
GUCY1A2GeneProductENSG00000152402 (Ensembl) "sGC" in source
GUCY1A3GeneProductENSG00000164116 (Ensembl) "sGC" in source
GUCY1B2GeneProductENSG00000293412 (Ensembl) "sGC" in source
MYLKGeneProductENSG00000065534 (Ensembl) "MLCK" in source
MyocytesPathwayWP5603 (WikiPathways)
Myosin-actin interactionPathwayWP4962 (WikiPathways)
NOMetaboliteCHEBI:16480 (ChEBI)
NOS3GeneProductENSG00000164867 (Ensembl) "eNOS" in source
NeuronsPathwayWP5602 (WikiPathways)
PDE3AGeneProductENSG00000172572 (Ensembl) "PDEs" in source
PDE3BGeneProductENSG00000152270 (Ensembl) "PDEs" in source
PDE4AGeneProductENSG00000065989 (Ensembl) "PDEs" in source
PDE4BGeneProductENSG00000184588 (Ensembl) "PDEs" in source
PDE4DGeneProductENSG00000113448 (Ensembl) "PDEs" in source
PPP1CBGeneProductENSG00000213639 (Ensembl) "MP" in source
PPP1R12AGeneProductENSG00000058272 (Ensembl) "MP" in source
PPP1R12CGeneProductENSG00000125503 (Ensembl) "MP" in source
RYR2GeneProductENSG00000198626 (Ensembl)
RYR3GeneProductENSG00000198838 (Ensembl)
VasodilationBiologicalProcessQ14859627 (Wikidata)
cAMPMetaboliteCHEBI:17489 (ChEBI)
cGMPMetaboliteCHEBI:16356 (ChEBI)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5601"