GPR55

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G protein-coupled receptor 55
Identifiers
SymbolsGPR55;
External IDsOMIM: 604107 MGI: 2685064 HomoloGene: 36184 IUPHAR: GPR55 GeneCards: GPR55 Gene
Orthologs
SpeciesHumanMouse
Entrez9290227326
EnsemblENSG00000135898ENSMUSG00000049608
UniProtQ9Y2T6Q14BV9
RefSeq (mRNA)NM_005683NM_001033290
RefSeq (protein)NP_005674NP_001028462
Location (UCSC)Chr 2:
231.48 - 231.5 Mb		Chr 1:
87.77 - 87.79 Mb
PubMed search[1][2]

G protein-coupled receptor 55 also known as GPR55 is a G protein-coupled receptor that in humans is encoded by the GPR55 gene.[1]

GPR55, along with GPR119 and GPR18, have been implicated as novel cannabinoid receptors.[2][3]

History

GPR55 was identified and cloned for the first time in 1999.[4] Later it was identified by an in silico screen as a putative cannabinoid receptor because of a similar amino acid sequence in the binding region.[5] Research groups from Glaxo Smith Kline and Astra Zeneca characterized the receptor extensively because it was hoped to be responsible for the blood pressure lowering properties of cannabinoids. GPR55 is indeed activated by endogenous, plant and synthetic cannabinoids but GPR-55 knockout mice generated by a research group from Glaxo Smith Kline showed no altered blood pressure regulation after administration of the cannabidiol-derivative abnormal cannabidiol.[6]

Signal cascade

GPR55 is coupled to the G-protein G13 and activation of the receptor leads to stimulation of rhoA, cdc42 and rac1.[7]

Pharmacology

GPR55 is activated by the plant cannabinoids Δ9-THC and cannabidiol,[8] and the endocannabinoids anandamide, 2-AG, noladin ether in the low nanomolar range. The synthetic cannabinoid CP-55940 is also able to activate the receptor[8] while the structurally unrelated cannabinoid mimic WIN 55,212-2 fails to activate the receptor.[6] Recent research suggests that lysophosphatidylinositol and its 2-arachidonoyl derivative may be the endogenous ligands for GPR55,[9][10][11] and the receptor appears likely to be a possible target for treatment of inflammation and pain as with the other cannabinoid receptors.[12][13]

This profile as a distinct non-CB1/CB2 receptor which responds to a variety of both endogenous and exogenous cannabinoid ligands, has led some groups to suggest GPR55 should be categorised as the CB3 receptor, and this re-classification may follow in time.[14][15][16][17] However this is complicated by the fact that another possible CB3 receptor has been discovered in the hippocampus, although its gene has not yet been cloned,[18] suggesting that there may be at least four cannabinoid receptors which will eventually be characterised.

Physiological function

The physiological role of GPR55 is unclear. Mice with a target deletion of the GPR55 gene show no specific phenotype.[6] GPR55 is widely expressed in the brain, especially in the cerebellum. It is expressed in the jejunum and ileum but apparently not more generally in the periphery.[8] Osteoblasts and osteoclasts express GPR55 and this has been shown to regulate bone cell function.[19]

References

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Further reading

40x30px This transmembrane receptor-related article is a stub. You can help ssf by expanding it.
Class A: Rhodopsin like
α1 (A, B, D) · α2 (A, B, C) · β1 · β2 · β3
Adenosine (A1, A2A, A2B, A3) · P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
(all but 5-HT3) 5-HT1 (A, B, D, E, F) · 5-HT2 (A, B, C) · 5-HT (4, 5A, 6, 7)
Other
Acetylcholine (M1, M2, M3, M4, M5) · Dopamine (D1, D2, D3, D4, D5) · Histamine (H1, H2, H3, H4) · Melatonin (1A, 1B, 1C) · TAAR (1, 2, 3, 5, 6, 8, 9)
Metabolites and
signaling molecules
CysLT (1, 2) · LTB4 (1, 2) · FPRL1 · OXE · Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) · Prostacyclin · Thromboxane
Other
Bile acid · Cannabinoid (CB1, CB2, GPR (18, 55, 119)) · EBI2 · Estrogen · Free fatty acid (1, 2, 3, 4) · Lactate  · Lysophosphatidic acid (1, 2, 3, 4, 5, 6)  · Lysophospholipid (1, 2, 3, 4, 5, 6, 7, 8) · Niacin (1, 2) · Oxoglutarate · PAF · Sphingosine-1-phosphate (1, 2, 3, 4, 5) · Succinate
Peptide
B/W (1, 2) · FF (1, 2) · S · Y (1, 2, 4, 5) · Neuromedin (B, U (1, 2)) · Neurotensin (1, 2)
Other
Miscellaneous
GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Other
Class B: Secretin like
GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Other
Class C: Metabotropic
glutamate / pheromone
TAS1R (1, 2, 3) · TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Other
Class F:
Frizzled / Smoothened
Frizzled
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Smoothened
  1. ↑ "Entrez Gene: GPR55 G protein-coupled receptor 55". 
  2. ↑ Brown AJ. (2007). "Novel cannabinoid receptors". Br J Pharmacol. 152 (5): 567–575. doi:10.1038/sj.bjp.0707481. PMC 2190013 Freely accessible. PMID 17906678. 
  3. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  4. ↑ Sawzdargo M, Nguyen T, Lee DK, Lynch KR, Cheng R, Heng HH, George SR, O'Dowd BF (1999). "Identification and cloning of three novel human G protein-coupled receptor genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain". Brain Res. Mol. Brain Res. 64 (2): 193–8. doi:10.1016/S0169-328X(98)00277-0. PMID 9931487. 
  5. ↑ Baker D, Pryce G, Davies WL, Hiley CR (2006). "In silico patent searching reveals a new cannabinoid receptor". Trends Pharmacol. Sci. 27 (1): 1–4. doi:10.1016/j.tips.2005.11.003. PMID 16318877. 
  6. ↑ 6.0 6.1 6.2 Johns DG, Behm DJ, Walker DJ, Ao Z, Shapland EM, Daniels DA, Riddick M, Dowell S, Staton PC, Green P, Shabon U, Bao W, Aiyar N, Yue TL, Brown AJ, Morrison AD, Douglas SA (2007). "The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects". Br. J. Pharmacol. 152 (5): 825–31. doi:10.1038/sj.bjp.0707419. PMC 2190033 Freely accessible. PMID 17704827. 
  7. ↑ Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K (2008). "GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current". Proc. Natl. Acad. Sci. U.S.A. 105 (7): 2699–704. doi:10.1073/pnas.0711278105. PMC 2268199 Freely accessible. PMID 18263732. 
  8. ↑ 8.0 8.1 8.2 Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ (2007). "The orphan receptor GPR55 is a novel cannabinoid receptor". Br. J. Pharmacol. 152 (7): 1092–101. doi:10.1038/sj.bjp.0707460. PMC 2095107 Freely accessible. PMID 17876302. 
  9. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  10. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  11. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  12. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  13. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  14. ↑ Overton H, Babbs A, Doel S, Fyfe M, Gardner L, Griffin G, Jackson H, Procter M, Rasamison C, Tang-Christensen M. Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metabolism 2003; 3(3):167-175.
  15. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  16. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  17. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  18. ↑ De Fonseca FR, Schneider M. The endogenous cannabinoid system and drug addiction: 20 years after the discovery of the CB1 receptor. Addiction Biology 2008; 13:143-146.
  19. ↑ Whyte LS, Ryberg E, Sims NA, Ridge SA, Mackie K, Greasley PJ, Ross RA, Rogers MJ. (2009). The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo. PNAS, 106: 16511–16516 (2009). "The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo". Proceedings of the National Academy of Sciences of the United States of America. 106 (38): 16511–6. doi:10.1073/pnas.0902743106. PMC 2737440 Freely accessible. PMID 19805329. 
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