Cannabinoid receptor

cannabinoid receptor 2
cannabinoid receptor 2
	Human cannabinoid receptor 2 (CB2) bound to agonist AM10257 (black). PDB: 5ZTY
Identifiers
Symbol	CNR2
NCBI gene	1269
HGNC	2160
OMIM	605051
Orthologs	1389
RefSeq	NM_001841
UniProt	P34972
Other data
Locus	Chr. 1 p
Structures
Search for
Structures	Swiss-model
Domains	InterPro

Search for
Structures	Swiss-model
Domains	InterPro

cannabinoid receptor 1
cannabinoid receptor 1
	Human cannabinoid receptor 1 (CB1) bound to tetrahydrocannabinol agonist AM11542 (black). PDB: 5XRA
Identifiers
Symbol	CNR1
Alt. symbols	CNR
NCBI gene	1268
HGNC	2159
OMIM	114610
Orthologs	7273
RefSeq	NM_033181
UniProt	P21554
Other data
Locus	Chr. 6 q14-q15
Structures
Search for
Structures	Swiss-model
Domains	InterPro

Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system of vertebrates– a class of cell membrane receptors in the G protein-coupled receptor superfamily.^[1]^[2]^[3]^[4] As is typical of G protein-coupled receptors, the cannabinoid receptors contain seven transmembrane spanning domains.^[5] Cannabinoid receptors are activated by three major groups of ligands:

Endocannabinoids;
Phytocannabinoids (plant-derived such as tetrahydrocannabinol (THC) produced by cannabis);
Synthetic cannabinoids (such as HU-210).

All endocannabinoids and phytocannabinoids are lipophilic.

There are two known subtypes of cannabinoid receptors, termed CB₁ and CB₂.^[6]^[7] The CB₁ receptor is expressed mainly in the brain (central nervous system or "CNS"), but also in the lungs, liver and kidneys. The CB₂ receptor is expressed mainly in the immune system, in hematopoietic cells,^[8] and in parts of the brain.^[9]

The protein sequences of CB₁ and CB₂ receptors are about 44% similar.^[10]^[11] When only the transmembrane regions of the receptors are considered, amino acid similarity between the two receptor subtypes is approximately 68%.^[5] In addition, minor variations in each receptor have been identified. Cannabinoids bind reversibly and stereo-selectively to the cannabinoid receptors. Subtype selective cannabinoids have been developed which theoretically may have advantages for treatment of certain diseases such as obesity.^[12]

Enzymes involved in biosynthesis/inactivation of endocannabinoids and endocannabinoid signaling in general (involving targets other than CB1/2-type receptors) occur throughout the animal kingdom.^[13]

^ Cite error: The named reference pmid12432948 was invoked but never defined (see the help page).
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^ Aizpurua-Olaizola O, Elezgarai I, Rico-Barrio I, Zarandona I, Etxebarria N, Usobiaga A (January 2017). "Targeting the endocannabinoid system: future therapeutic strategies". Drug Discovery Today. 22 (1): 105–110. doi:10.1016/j.drudis.2016.08.005. PMID 27554802. S2CID 3460960. Archived from the original on 2023-01-27. Retrieved 2022-10-19.
^ ^a ^b Cite error: The named reference pmid7556170 was invoked but never defined (see the help page).
^ Cite error: The named reference pmid2165569 was invoked but never defined (see the help page).
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^ Pacher P, Mechoulam R (April 2011). "Is lipid signaling through cannabinoid 2 receptors part of a protective system?". Progress in Lipid Research. 50 (2): 193–211. doi:10.1016/j.plipres.2011.01.001. PMC 3062638. PMID 21295074.
^ Jordan CJ, Xi ZX (March 2019). "Progress in brain cannabinoid CB2 receptor research: From genes to behavior". Neuroscience and Biobehavioral Reviews. 98: 208–220. doi:10.1016/j.neubiorev.2018.12.026. PMC 6401261. PMID 30611802.
^ Latek D, Kolinski M, Ghoshdastider U, Debinski A, Bombolewski R, Plazinska A, et al. (September 2011). "Modeling of ligand binding to G protein coupled receptors: cannabinoid CB1, CB2 and adrenergic β 2 AR". Journal of Molecular Modeling. 17 (9): 2353–66. doi:10.1007/s00894-011-0986-7. PMID 21365223. S2CID 28365397.
^ Cite error: The named reference pmid7689702 was invoked but never defined (see the help page).
^ Kyrou I, Valsamakis G, Tsigos C (November 2006). "The endocannabinoid system as a target for the treatment of visceral obesity and metabolic syndrome". Annals of the New York Academy of Sciences. 1083 (1): 270–305. Bibcode:2006NYASA1083..270K. doi:10.1196/annals.1367.024. PMID 17148745. S2CID 23486551.
^ Elphick MR (December 2012). "The evolution and comparative neurobiology of endocannabinoid signalling". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 367 (1607): 3201–15. doi:10.1098/rstb.2011.0394. PMC 3481536. PMID 23108540.

[pmid12432948-1] Cite error: The named reference pmid12432948 was invoked but never defined (see the help page).

[pmid18426493-2] Cite error: The named reference pmid18426493 was invoked but never defined (see the help page).

[pmid19273110-3] Cite error: The named reference pmid19273110 was invoked but never defined (see the help page).

[4] Aizpurua-Olaizola O, Elezgarai I, Rico-Barrio I, Zarandona I, Etxebarria N, Usobiaga A (January 2017). "Targeting the endocannabinoid system: future therapeutic strategies". Drug Discovery Today. 22 (1): 105–110. doi:10.1016/j.drudis.2016.08.005. PMID 27554802. S2CID 3460960. Archived from the original on 2023-01-27. Retrieved 2022-10-19.

[pmid7556170-5] Cite error: The named reference pmid7556170 was invoked but never defined (see the help page).

[pmid2165569-6] Cite error: The named reference pmid2165569 was invoked but never defined (see the help page).

[pmid1718258-7] Cite error: The named reference pmid1718258 was invoked but never defined (see the help page).

[pmid21295074-8] Pacher P, Mechoulam R (April 2011). "Is lipid signaling through cannabinoid 2 receptors part of a protective system?". Progress in Lipid Research. 50 (2): 193–211. doi:10.1016/j.plipres.2011.01.001. PMC 3062638. PMID 21295074.

[pmid30611802-9] Jordan CJ, Xi ZX (March 2019). "Progress in brain cannabinoid CB2 receptor research: From genes to behavior". Neuroscience and Biobehavioral Reviews. 98: 208–220. doi:10.1016/j.neubiorev.2018.12.026. PMC 6401261. PMID 30611802.

[latek-10] Latek D, Kolinski M, Ghoshdastider U, Debinski A, Bombolewski R, Plazinska A, et al. (September 2011). "Modeling of ligand binding to G protein coupled receptors: cannabinoid CB1, CB2 and adrenergic β 2 AR". Journal of Molecular Modeling. 17 (9): 2353–66. doi:10.1007/s00894-011-0986-7. PMID 21365223. S2CID 28365397.

[pmid7689702-11] Cite error: The named reference pmid7689702 was invoked but never defined (see the help page).

[pmid17148745-12] Kyrou I, Valsamakis G, Tsigos C (November 2006). "The endocannabinoid system as a target for the treatment of visceral obesity and metabolic syndrome". Annals of the New York Academy of Sciences. 1083 (1): 270–305. Bibcode:2006NYASA1083..270K. doi:10.1196/annals.1367.024. PMID 17148745. S2CID 23486551.

[13] Elphick MR (December 2012). "The evolution and comparative neurobiology of endocannabinoid signalling". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 367 (1607): 3201–15. doi:10.1098/rstb.2011.0394. PMC 3481536. PMID 23108540.

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