GPR55: Wikis


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G protein-coupled receptor 55
Symbols GPR55;
External IDs OMIM604107 MGI2685064 HomoloGene36184 IUPHAR: GPR55 GeneCards: GPR55 Gene
Species Human Mouse
Entrez 9290 227326
Ensembl ENSG00000135898 ENSMUSG00000049608
UniProt Q9Y2T6 Q14BV9
RefSeq (mRNA) NM_005683 NM_001033290
RefSeq (protein) NP_005674 NP_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 which in humans is encoded by the GPR55 gene.[1]

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



GPR55 was identified and cloned for the first time in 1999.[3] 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.[4] 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.[5]

Signal cascade

GPR55 is coupled to the G-protein G13 and activation of the receptor leads to stimulation of rhoA, cdc42 and rac1.[6]


GPR55 is activated by the plant cannabinoids Δ9-THC and cannabidiol,[7] 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[7] while the structurally unrelated cannabinoid mimic WIN 55,212-2 fails to activate the receptor.[5] Recent research suggests that lysophosphatidylinositol and its 2-arachidonoyl derivative may be the endogenous ligands for GPR55,[8][9][10] and the receptor appears likely to be a possible target for treatment of inflammation and pain as with the other cannabinoid receptors.[11][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] 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,[15] 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.[5] 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.[7] Osteoblasts and osteoclasts express GPR55 and this has been shown to regulate bone cell function.[16]


  1. ^ "Entrez Gene: GPR55 G protein-coupled receptor 55".  
  2. ^ Brown AJ. (2007). "Novel cannabinoid receptors.". Br J Pharmacol. 152 (5): 567–575. PMID 17906678.  
  3. ^ 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.  
  4. ^ 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/ PMID 16318877.  
  5. ^ a b c 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. PMID 17704827.  
  6. ^ 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. PMID 18263732.  
  7. ^ a b c 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. PMID 17876302.  
  8. ^ Oka S, Nakajima K, Yamashita A, Kishimoto S, Sugiura T (November 2007). "Identification of GPR55 as a lysophosphatidylinositol receptor". Biochemical and Biophysical Research Communications 362 (4): 928–34. doi:10.1016/j.bbrc.2007.08.078. PMID 17765871.  
  9. ^ Henstridge CM, Balenga NA, Ford LA, Ross RA, Waldhoer M, Irving AJ (January 2009). "The GPR55 ligand L-alpha-lysophosphatidylinositol promotes RhoA-dependent Ca2+ signaling and NFAT activation". The FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology 23 (1): 183–93. doi:10.1096/fj.08-108670. PMID 18757503.  
  10. ^ Oka S, Toshida T, Maruyama K, Nakajima K, Yamashita A, Sugiura T (January 2009). "2-Arachidonoyl-sn-glycero-3-phosphoinositol: a possible natural ligand for GPR55". Journal of Biochemistry 145 (1): 13–20. doi:10.1093/jb/mvn136. PMID 18845565.  
  11. ^ Staton PC, Hatcher JP, Walker DJ, Morrison AD, Shapland EM, Hughes JP, Chong E, Mander PK, Green PJ, Billinton A, Fulleylove M, Lancaster HC, Smith JC, Bailey LT, Wise A, Brown AJ, Richardson JC, Chessell IP (September 2008). "The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain". Pain 139 (1): 225–36. doi:10.1016/j.pain.2008.04.006. PMID 18502582.  
  12. ^ Kress M, Kuner R (March 2009). "Mode of action of cannabinoids on nociceptive nerve endings". Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. doi:10.1007/s00221-009-1762-0. PMID 19306092.  
  13. ^ Ross RA (March 2009). "The enigmatic pharmacology of GPR55". Trends in Pharmacological Sciences 30 (3): 156–63. doi:10.1016/ PMID 19233486.  
  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. ^ 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.
  16. ^ 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. doi:10.1073/pnas.0902743106.  

Further reading

  • Sawzdargo M, Nguyen T, Lee DK, et al. (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.  
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.  
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMID 15489334.  


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