GPR55

G protein-coupled receptor 55, also known as GPR55, is a human gene which encodes the protein for the GPR-55 receptor.cite web | title = Entrez Gene: GPR55 G protein-coupled receptor 55| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9290| accessdate = ]

History

GPR55 was identified and cloned for the first time in 1999.cite journal | author = Sawzdargo M, Nguyen T, Lee DK, Lynch KR, Cheng R, Heng HH, George SR, O'Dowd BF | title = Identification and cloning of three novel human G protein-coupled receptor genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain | journal = Brain Res. Mol. Brain Res. | volume = 64 | issue = 2 | pages = 193–8 | year = 1999 | pmid = 9931487 | doi = 10.1016/S0169-328X(98)00277-0 | issn = ] 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.cite journal |author=Baker D, Pryce G, Davies WL, Hiley CR |title=In silico patent searching reveals a new cannabinoid receptor |journal=Trends Pharmacol. Sci. |volume=27 |issue=1 |pages=1–4 |year=2006 |pmid=16318877 |doi=10.1016/j.tips.2005.11.003 ] 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.cite journal | author = 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 | title = The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects | journal = Br. J. Pharmacol. | volume = 152 | issue = 5 | pages = 825–31 | year = 2007 | pmid = 17704827 | doi = 10.1038/sj.bjp.0707419 | issn = ]

Signal cascade

GPR55 is coupled to the G-protein G₁₃ and activation of the receptor leads to stimulation of rhoA, cdc42 and rac1.cite journal | author = Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K | title = GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 105 | issue = 7 | pages = 2699–704 | year = 2008 | pmid = 18263732 | doi = 10.1073/pnas.0711278105 | issn = ]

Pharmacology

GPR55 is activated by the plant cannabinoids Δ⁹-THC and cannabidiol,cite journal | author = Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ | title = The orphan receptor GPR55 is a novel cannabinoid receptor | journal = Br. J. Pharmacol. | volume = 152 | issue = 7 | pages = 1092–101 | year = 2007 | pmid = 17876302 | doi = 10.1038/sj.bjp.0707460 | issn = ] 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 while the structurally unrelated cannabinoid mimic WIN 55,212-2 fails to activate the receptor.

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. [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.] 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, [ [http://www.zi-mannheim.de/fileadmin/user_upload/redakteure/psychopharma/De_Fonseca_2008.pdf 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.] ] 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.cite journal | author = 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 | title = The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects | journal = Br. J. Pharmacol. | volume = 152 | issue = 5 | pages = 825–31 | year = 2007 | pmid = 17704827 | doi = 10.1038/sj.bjp.0707419 | issn = ] GPR55 is widely expressed in the brain, especially in the cerebellum. Except for the jejunum and ileum it is not expressed in the periphery.cite journal | author = Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ | title = The orphan receptor GPR55 is a novel cannabinoid receptor | journal = Br. J. Pharmacol. | volume = 152 | issue = 7 | pages = 1092–101 | year = 2007 | pmid = 17876302 | doi = 10.1038/sj.bjp.0707460 | issn = ]

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Sawzdargo M, Nguyen T, Lee DK, "et al." |title=Identification and cloning of three novel human G protein-coupled receptor genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain. |journal=Brain Res. Mol. Brain Res. |volume=64 |issue= 2 |pages= 193–8 |year= 1999 |pmid= 9931487 |doi=
*cite journal | author=Strausberg RL, Feingold EA, Grouse LH, "et al." |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899
*cite journal | author=Gerhard DS, Wagner L, Feingold EA, "et al." |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504

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