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Encyclopedia of Signaling Molecules pp 2200–2217Cite as

GPR55

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Synonyms

G protein-coupled receptor 55; Gm218; LPIR1

Historical Background

G protein-coupled receptor 55 (GPR55) was first cloned in 1999 and is a 319 amino acid seven transmembrane G protein-coupled receptor (GPCR) that is mapped to chromosome 2q37 (human) (Sawzdargo et al. 1999). It displays features common with other Family A GPCRs including a short extracellular N-terminal and C-terminal tail and contains two highly conserved extracellular cysteine residues that form disulfide bonds to help stabilize the receptor structure. Glycosylation sites in its N-terminus are present, while its intracellular loops and C-terminal tail have a number of potential phosphorylation sites. Orthologues for GPR55 have been found in a number of mammalian species including rat, mouse, dog, cow, chimpanzee, and human (Baker et al. 2006) (Figs. 1 and 2).

GPR55, Fig. 1
figure 881 figure 881

Snake plot diagram of the human GPR55 receptor. GPR55 is a seven transmembrane spanning receptor with an extracellular N-terminal domain...

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References

  • Baker D, Pryce G, Davies WL, Hiley CR. In silico patent searching reveals a new cannabinoid receptor. Trends Pharmacol Sci. 2006;27(1):1–4.

    Article  PubMed  CAS  Google Scholar 

  • Balenga NA, Aflaki E, Kargl J, Platzer W, Schroder R, Blattermann S, Kostenis E, Brown AJ, Heinemann A, Waldhoer M. GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils. Cell Res. 2011;21(10):1452–69.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Balenga NA, Martinez-Pinilla E, Kargl J, Schroder R, Peinhaupt M, Platzer W, Balint Z, Zamarbide M, Dopeso-Reyes IG, Ricobaraza A, Perez-Ortiz JM, Kostenis E, Waldhoer M, Heinemann A, Franco R. Heteromerization of GPR55 and cannabinoid CB2 receptors modulates signalling. Br J Pharmacol. 2014;171(23):5387–406.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chiurchiu V, Lanuti M, De Bardi M, Battistini L, Maccarrone M. The differential characterization of GPR55 receptor in human peripheral blood reveals a distinctive expression in monocytes and NK cells and a proinflammatory role in these innate cells. Int Immunol. 2015;27(3):153–60.

    Article  PubMed  CAS  Google Scholar 

  • Henstridge CM, Balenga NA, Ford LA, Ross RA, Waldhoer M, Irving AJ. The GPR55 ligand L-alpha-lysophosphatidylinositol promotes RhoA-dependent Ca2+ signaling and NFAT activation. FASEB J : Off Publ Fed Am Soc Exp Biol. 2009;23(1):183–93.

    Article  CAS  Google Scholar 

  • Henstridge CM, Balenga NA, Kargl J, Andradas C, Brown AJ, Irving A, Sanchez C, Waldhoer M. Minireview: recent developments in the physiology and pathology of the lysophosphatidylinositol-sensitive receptor GPR55. Mol Endocrinol. 2011;25(11):1835–48.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Henstridge CM, Balenga NA, Schroder R, Kargl JK, Platzer W, Martini L, Arthur S, Penman J, Whistler JL, Kostenis E, Waldhoer M, Irving AJ. GPR55 ligands promote receptor coupling to multiple signalling pathways. Br J Pharmacol. 2010;160(3):604–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jarai Z, Wagner JA, Varga K, Lake KD, Compton DR, Martin BR, Zimmer AM, Bonner TI, Buckley NE, Mezey E, Razdan RK, Zimmer A, Kunos G. Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors. Proc Natl Acad Sci U S A. 1999;96(24):14136–41.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jenkin KA, McAinch AJ, Grinfeld E, Hryciw DH. Role for cannabinoid receptors in human proximal tubular hypertrophy. Cell Physiol Biochem : Int J Exp Cell Physiol Biochem Pharmacol. 2010;26(6):879–86.

    Article  CAS  Google Scholar 

  • 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. The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. Br J Pharmacol. 2007;152(5):825–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kapur A, Zhao P, Sharir H, Bai Y, Caron MG, Barak LS, Abood ME. Atypical responsiveness of the orphan receptor GPR55 to cannabinoid ligands. J Biol Chem. 2009;284(43):29817–27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kargl J, Andersen L, Hasenohrl C, Feuersinger D, Stancic A, Fauland A, Magnes C, El-Heliebi A, Lax S, Uranitsch S, Haybaeck J, Heinemann A, Schicho R. GPR55 promotes migration and adhesion of colon cancer cells indicating a role in metastasis. Br J Pharmacol. 2016;173(1):142–54.

    Article  PubMed  CAS  Google Scholar 

  • Kargl J, Balenga N, Parzmair GP, Brown AJ, Heinemann A, Waldhoer M. The cannabinoid receptor CB1 modulates the signaling properties of the lysophosphatidylinositol receptor GPR55. J Biol Chem. 2012;287(53):44234–48.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kargl J, Brown AJ, Andersen L, Dorn G, Schicho R, Waldhoer M, Heinemann A. A selective antagonist reveals a potential role of G protein-coupled receptor 55 in platelet and endothelial cell function. J Pharmacol Exp Ther. 2013;346(1):54–66.

    Article  PubMed  CAS  Google Scholar 

  • Kotsikorou E, Madrigal KE, Hurst DP, Sharir H, Lynch DL, Heynen-Genel S, Milan LB, Chung TD, Seltzman HH, Bai Y, Caron MG, Barak L, Abood ME, Reggio PH. Identification of the GPR55 agonist binding site using a novel set of high-potency GPR55 selective ligands. Biochemistry. 2011;50(25):5633–47.

    Article  PubMed  CAS  Google Scholar 

  • Kotsikorou E, Sharir H, Shore DM, Hurst DP, Lynch DL, Madrigal KE, Heynen-Genel S, Milan LB, Chung TD, Seltzman HH, Bai Y, Caron MG, Barak LS, Croatt MP, Abood ME, Reggio PH. Identification of the GPR55 antagonist binding site using a novel set of high-potency GPR55 selective ligands. Biochemistry. 2013;52(52):9456–69.

    Article  PubMed  CAS  Google Scholar 

  • Kremshofer J, Siwetz M, Berghold VM, Lang I, Huppertz B, Gauster M. A role for GPR55 in human placental venous endothelial cells. Histochem Cell Biol. 2015;144(1):49–58.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K. GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci U S A. 2008;105(7):2699–704.

    Article  PubMed  PubMed Central  Google Scholar 

  • Leyva-Illades D, Demorrow S. Orphan G protein receptor GPR55 as an emerging target in cancer therapy and management. Cancer Manag Res. 2013;5:147–55.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Li K, Feng JY, Li YY, Yuece B, Lin XH, Yu LY, Li YN, Feng YJ, Storr M. Anti-inflammatory role of cannabidiol and O-1602 in cerulein-induced acute pancreatitis in mice. Pancreas. 2013a;42(1):123–9.

    Article  PubMed  CAS  Google Scholar 

  • Li K, Fichna J, Schicho R, Saur D, Bashashati M, Mackie K, Li Y, Zimmer A, Goke B, Sharkey KA, Storr M. A role for O-1602 and G protein-coupled receptor GPR55 in the control of colonic motility in mice. Neuropharmacology. 2013b;71:255–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lin XH, Wei DD, Wang HC, Wang B, Bai CY, Wang YQ, Li GE, Li HP, Ren XQ. Role of orphan G protein-coupled receptor 55 in diabetic gastroparesis in mice. Sheng Li Xue Bao : [Acta Physiol Sin]. 2014;66(3):332–40.

    CAS  Google Scholar 

  • Lin XH, Yuece B, Li YY, Feng YJ, Feng JY, Yu LY, Li K, Li YN, Storr M. A novel CB receptor GPR55 and its ligands are involved in regulation of gut movement in rodents. Neurogastroenterol Motil : Off J Eur Gastrointest Motil Soc. 2011;23(9):862–e342.

    Article  CAS  Google Scholar 

  • Martinez-Pinilla E, Reyes-Resina I, Onatibia-Astibia A, Zamarbide M, Ricobaraza A, Navarro G, Moreno E, Dopeso-Reyes IG, Sierra S, Rico AJ, Roda E, Lanciego JL, Franco R. CB1 and GPR55 receptors are co-expressed and form heteromers in rat and monkey striatum. Exp Neurol. 2014;261:44–52.

    Article  PubMed  CAS  Google Scholar 

  • McHugh D, Hu SS, Rimmerman N, Juknat A, Vogel Z, Walker JM, Bradshaw HB. N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor. BMC Neurosci. 2010;11:44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • McHugh D, Page J, Dunn E, Bradshaw HB. Delta(9) -Tetrahydrocannabinol and N-arachidonyl glycine are full agonists at GPR18 receptors and induce migration in human endometrial HEC-1B cells. Br J Pharmacol. 2012;165(8):2414–24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • McKillop AM, Moran BM, Abdel-Wahab YH, Flatt PR. Evaluation of the insulin releasing and antihyperglycaemic activities of GPR55 lipid agonists using clonal beta-cells, isolated pancreatic islets and mice. Br J Pharmacol. 2013;170(5):978–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Meadows A, Lee JH, Wu CS, Wei Q, Pradhan G, Yafi M, Lu HC, Sun Y. Deletion of G-protein-coupled receptor 55 promotes obesity by reducing physical activity. Int J Obes. 2016;40(3):417–24.

    Article  CAS  Google Scholar 

  • Moreno-Navarrete JM, Catalan V, Whyte L, Diaz-Arteaga A, Vazquez-Martinez R, Rotellar F, Guzman R, Gomez-Ambrosi J, Pulido MR, Russell WR, Imbernon M, Ross RA, Malagon MM, Dieguez C, Fernandez-Real JM, Fruhbeck G, Nogueiras R. The L-alpha-lysophosphatidylinositol/GPR55 system and its potential role in human obesity. Diabetes. 2012;61(2):281–91.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Moreno E, Andradas C, Medrano M, Caffarel MM, Perez-Gomez E, Blasco-Benito S, Gomez-Canas M, Pazos MR, Irving AJ, Lluis C, Canela EI, Fernandez-Ruiz J, Guzman M, McCormick PJ, Sanchez C. Targeting CB2-GPR55 receptor heteromers modulates cancer cell signaling. J Biol Chem. 2014;289(32):21960–72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Oka S, Kimura S, Toshida T, Ota R, Yamashita A, Sugiura T. Lysophosphatidylinositol induces rapid phosphorylation of p38 mitogen-activated protein kinase and activating transcription factor 2 in HEK293 cells expressing GPR55 and IM-9 lymphoblastoid cells. J Biochem. 2010;147(5):671–8.

    Article  PubMed  CAS  Google Scholar 

  • Oka S, Nakajima K, Yamashita A, Kishimoto S, Sugiura T. Identification of GPR55 as a lysophosphatidylinositol receptor. Biochem Biophys Res Commun. 2007;362(4):928–34.

    Article  PubMed  CAS  Google Scholar 

  • Omasits U, Ahrens CH, Muller S, Wollscheid B. Protter: interactivate protein feature visualization and integration with experimental proteomic. Bioinformatics. 2013;30(6):884–86.

    Article  PubMed  CAS  Google Scholar 

  • Overton HA, Fyfe MC, Reynet C. GPR119, a novel G protein-coupled receptor target for the treatment of type 2 diabetes and obesity. Br J Pharmacol. 2008;153(Suppl 1):S76–81.

    PubMed  CAS  Google Scholar 

  • Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, Mackie K, Mechoulam R, Ross RA. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB(1) and CB(2). Pharmacol Rev. 2010;62(4):588–631.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Romero-Zerbo SY, Rafacho A, Diaz-Arteaga A, Suarez J, Quesada I, Imbernon M, Ross RA, Dieguez C, Rodriguez de Fonseca F, Nogueiras R, Nadal A, Bermudez-Silva FJ. A role for the putative cannabinoid receptor GPR55 in the islets of Langerhans. J Endocrinol. 2011;211(2):177–85.

    Article  PubMed  CAS  Google Scholar 

  • Ryberg E, Larsson N, Sjogren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol. 2007;152(7):1092–101.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sawzdargo M, Nguyen T, Lee DK, Lynch KR, Cheng R, Heng HH, George SR, O'Dowd BF. 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. 1999;64(2):193–8.

    Article  PubMed  CAS  Google Scholar 

  • Schicho R, Bashashati M, Bawa M, McHugh D, Saur D, Hu HM, Zimmer A, Lutz B, Mackie K, Bradshaw HB, McCafferty DM, Sharkey KA, Storr M. The atypical cannabinoid O-1602 protects against experimental colitis and inhibits neutrophil recruitment. Inflamm Bowel Dis. 2011;17(8):1651–64.

    Article  PubMed  Google Scholar 

  • Stancic A, Jandl K, Hasenohrl C, Reichmann F, Marsche G, Schuligoi R, Heinemann A, Storr M, Schicho R. The GPR55 antagonist CID16020046 protects against intestinal inflammation. Neurogastroenterol Motil Off J Euro Gastrointest Motil Soc. 2015;27(10):1432–45.

    Article  CAS  Google Scholar 

  • 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. The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain. Pain. 2008;139(1):225–36.

    Article  PubMed  CAS  Google Scholar 

  • Wagner JA, Varga K, Jarai Z, Kunos G. Mesenteric vasodilation mediated by endothelial anandamide receptors. Hypertension. 1999;33(1 Pt 2):429–34.

    Article  PubMed  CAS  Google Scholar 

  • Waldeck-Weiermair M, Zoratti C, Osibow K, Balenga N, Goessnitzer E, Waldhoer M, Malli R, Graier WF. Integrin clustering enables anandamide-induced Ca2+ signaling in endothelial cells via GPR55 by protection against CB1-receptor-triggered repression. J Cell Sci. 2008;121(Pt 10):1704–17.

    Article  PubMed  CAS  Google Scholar 

  • Whyte LS, Ryberg E, Sims NA, Ridge SA, Mackie K, Greasley PJ, Ross RA, Rogers MJ. The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo. Proc Natl Acad Sci U S A. 2009;106(38):16511–6.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

A.C. Simcocks was supported by Australian Rotary Health and the Rotary Club of Ballarat South.

D.S. Hutchinson is supported by a National Health and Medical Research Council of Australia Career Development Fellowship.

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Authors and Affiliations

  1. Centre for Chronic Diseases, College of Health and Biomedicine, Victoria University, St Albans Campus, Melbourne, 8001, VIC, Australia

    A. C. Simcocks, L. O’Keefe, D. H. Hryciw & M. L. Mathai

  2. School of Natural Sciences, Griffith University, Nathan, QLD, 4111, Australia

    D. H. Hryciw

  3. The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia

    M. L. Mathai

  4. Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, VIC, Australia

    D. S. Hutchinson

  5. Centre for Chronic Diseases, College of Health and Biomedicine, Australian Institute for Musculoskeletal Science, Victoria University, St Albans Campus, Melbourne, 8001, VIC, Australia

    Andrew J. McAinch

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  1. A. C. Simcocks
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  2. L. O’Keefe
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  3. D. H. Hryciw
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  4. M. L. Mathai
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  5. D. S. Hutchinson
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  6. Andrew J. McAinch
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Corresponding author

Correspondence to Andrew J. McAinch .

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Editors and Affiliations

  1. Department of Molecular Science and Technology, Ajou University, Suwon, Korea

    Sangdun Choi

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Simcocks, A.C., O’Keefe, L., Hryciw, D.H., Mathai, M.L., Hutchinson, D.S., McAinch, A.J. (2018). GPR55. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101626

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