Cannabinoid receptor

CB1 and CB2 structures
cannabinoid receptor 1
Human cannabinoid receptor 1 (CB1) bound to tetrahydrocannabinol agonist AM11542 (black). PDB: 5XRA​
Identifiers
SymbolCNR1
Alt. symbolsCNR
NCBI gene1268
HGNC2159
OMIM114610
Orthologs7273
RefSeqNM_033181
UniProtP21554
Other data
LocusChr. 6 q14-q15
Search for
StructuresSwiss-model
DomainsInterPro
cannabinoid receptor 2
Human cannabinoid receptor 2 (CB2) bound to agonist AM10257 (black). PDB: 5ZTY​
Identifiers
SymbolCNR2
NCBI gene1269
HGNC2160
OMIM605051
Orthologs1389
RefSeqNM_001841
UniProtP34972
Other data
LocusChr. 1 p
Search for
StructuresSwiss-model
DomainsInterPro
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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:

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]

  1. ^ Cite error: The named reference pmid12432948 was invoked but never defined (see the help page).
  2. ^ Cite error: The named reference pmid18426493 was invoked but never defined (see the help page).
  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.
  5. ^ a b Cite error: The named reference pmid7556170 was invoked but never defined (see the help page).
  6. ^ Cite error: The named reference pmid2165569 was invoked but never defined (see the help page).
  7. ^ Cite error: The named reference pmid1718258 was invoked but never defined (see the help page).
  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.
  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.
  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.
  11. ^ Cite error: The named reference pmid7689702 was invoked but never defined (see the help page).
  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.