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 Hu

Activity

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Organisms

Homo sapiens

Communities

Diseases

Annotations

Pathway Ontology

cannabinoid signaling pathway xenobiotic metabolic pathway

Cell Type Ontology

leukocyte neuron

Participants

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

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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