Cannabinoid receptor signaling (WP3869)
Homo sapiens
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
Authors
Friederike Ehrhart , Martina Summer-Kutmon , Denise Slenter , Irene Hemel , and Finterly HuActivity
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Organisms
Homo sapiensCommunities
DiseasesAnnotations
Pathway Ontology
cannabinoid signaling pathway xenobiotic metabolic pathwayCell Type Ontology
leukocyte neuron| Label | Type | Compact URI | Comment |
|---|---|---|---|
| 11-OH-THC | Metabolite | hmdb:HMDB0060906 | |
| Phosphatidylethanolamine | Metabolite | hmdb:HMDB0060501 | |
| cAMP | Metabolite | hmdb:HMDB0000058 | |
| NAPE | Metabolite | chebi:61232 | |
| Arachidonic acid | Metabolite | hmdb:HMDB0001043 | |
| THC | Metabolite | hmdb:HMDB0041865 | |
| 1''-hydroxycannabidiol | Metabolite | chebi:133056 | |
| 2-arachidonoylglycerol | Metabolite | hmdb:HMDB0004666 | |
| Glutamate | Metabolite | hmdb:HMDB0000148 | |
| Calcium | Metabolite | hmdb:HMDB0000464 | |
| GABA | Metabolite | hmdb:HMDB0000112 | |
| CBD | Metabolite | chebi:69478 | |
| ATP | Metabolite | hmdb:HMDB0000538 | |
| AEA | Metabolite | hmdb:HMDB0004080 | |
| COOH-THC | Metabolite | chebi:77273 | |
| 2''-hydroxycannabidiol | Metabolite | chebi:133058 | |
| 3''-hydroxycannabidiol | Metabolite | chebi:133059 | |
| 4''-hydroxycannabidiol | Metabolite | chebi:133055 | |
| 5''-hydroxycannabidiol | Metabolite | chebi:133062 | |
| 6a-hydroxycannabidiol | Metabolite | chebi:133049 | |
| 6b-hydroxycannabidiol | Metabolite | chebi:133052 | |
| 7-hydroxycannabidiol | Metabolite | chebi:133053 | |
| CYP3A4 | GeneProduct | ensembl:ENSG00000160868 | |
| CYP2C19 | GeneProduct | ensembl:ENSG00000165841 | |
| PRKACB | GeneProduct | ensembl:ENSG00000142875 | |
| MAPK11 | GeneProduct | uniprot:Q15759 | |
| PRKACA | GeneProduct | ensembl:ENSG00000072062 | |
| MAPK9 | GeneProduct | uniprot:P45984 | |
| MAPK10 | GeneProduct | uniprot:P53779 | |
| MAPK14 | GeneProduct | uniprot:Q16539 | |
| MAPK8 | GeneProduct | uniprot:P45983 | |
| MAPK12 | GeneProduct | uniprot:P53778 | |
| ADCY1 | GeneProduct | ensembl:ENSG00000164742 | |
| MAPK3 | GeneProduct | uniprot:P27361 | |
| PRKAR1A | GeneProduct | ensembl:ENSG00000108946 | |
| PRKAR2B | GeneProduct | ensembl:ENSG00000005249 | |
| MAPK1 | GeneProduct | uniprot:P28482 | |
| PRKAR1B | GeneProduct | ensembl:ENSG00000188191 | |
| PRKACG | GeneProduct | ensembl:ENSG00000165059 | |
| MAPK13 | GeneProduct | uniprot:O15264 | |
| PRKAR2A | GeneProduct | ena.embl:ENSG00000114302 | |
| CNR1 | GeneProduct | ensembl:ENSG00000118432 | |
| CYP2C9 | GeneProduct | ensembl:ENSG00000138109 | |
| MAPK | GeneProduct | eccode:2.7.11.24 | |
| DAGLB | GeneProduct | ensembl:ENSG00000164535 | |
| AHR | GeneProduct | ensembl:ENSG00000106546 | |
| NAPEPLD | GeneProduct | ensembl:ENSG00000161048 | |
| ADCY7 | GeneProduct | ensembl:ENSG00000121281 | |
| DAGLA | GeneProduct | ensembl:ENSG00000134780 | |
| FAAH | GeneProduct | ensembl:ENSG00000117480 | |
| ADORA2A | GeneProduct | ensembl:ENSG00000128271 | |
| CNR2 | GeneProduct | ensembl:ENSG00000188822 | |
| CYP1A1 | GeneProduct | ensembl:ENSG00000140465 |
References
- Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. Carrier EJ, Auchampach JA, Hillard CJ. Proc Natl Acad Sci U S A. 2006 May 16;103(20):7895–900. PubMed Europe PMC Scholia
- Identification of cytochrome P450 enzymes responsible for metabolism of cannabidiol by human liver microsomes. Jiang R, Yamaori S, Takeda S, Yamamoto I, Watanabe K. Life Sci. 2011 Aug 1;89(5–6):165–70. PubMed Europe PMC Scholia
- Endocannabinoids via CB₁ receptors act as neurogenic niche cues during cortical development. Díaz-Alonso J, Guzmán M, Galve-Roperh I. Philos Trans R Soc Lond B Biol Sci. 2012 Dec 5;367(1607):3229–41. PubMed Europe PMC Scholia
- Cannabidiol induces expression of human cytochrome P450 1A1 that is possibly mediated through aryl hydrocarbon receptor signaling in HepG2 cells. Yamaori S, Kinugasa Y, Jiang R, Takeda S, Yamamoto I, Watanabe K. Life Sci. 2015 Sep 1;136:87–93. PubMed Europe PMC Scholia
- Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Laprairie RB, Bagher AM, Kelly MEM, Denovan-Wright EM. Br J Pharmacol. 2015 Oct;172(20):4790–805. PubMed Europe PMC Scholia
- Pharmacokinetic Drug Interactions with Tobacco, Cannabinoids and Smoking Cessation Products. Anderson GD, Chan LN. Clin Pharmacokinet. 2016 Nov;55(11):1353–68. PubMed Europe PMC Scholia