GPR55

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G protein-spregnuti receptor 55
Identifikatori
SimboliGPR55;
Vanjski IDOMIM: 604107 MGI: 2685064 HomoloGene: 36184 IUPHAR: GPR55 GeneCards: GPR55 Gene
Ontologija gena
Molekularna funkcija • aktivnost rodopsinu sličnog receptora
• receptorska aktivnost
Celularna komponenta • integralno sa ćelijskom membranom
• membrana
Biološki proces • prenos signala
• signalni put G-protein spregnutog receptora
Ortolozi
VrstaČovekMiš
Entrez9290227326
EnsemblENSG00000135898ENSMUSG00000049608
UniProtQ9Y2T6Q14BV9
RefSeq (mRNA)NM_005683NM_001033290
RefSeq (protein)NP_005674NP_001028462
Lokacija (UCSC)Chr 2:
231.48 - 231.5 Mb		Chr 1:
87.77 - 87.79 Mb
PubMed pretraga[1][2]

GPR55, G protein-coupled receptor 55, je G protein-spregnuti receptor koji je kod čoveka kodiran GPR55 genom.[1]

Za GPR55, GPR119 i GPR18, se smatra da su kanabinoidni receptori.[2][3]

Istorija

GPR55 je bio identifikovan i kloniran prvi put 1999. godine.[4] Kasnije je bio identifikovan jednim in silico testom kao potencijalni kanabinoidni receptor zbog njegove slične aminokiselinske sekvence u regionu vezivanja.[5]

Istraživačke grupe kompanija GlaksoSmitKlajn i AstraZeneka su detaljno karakterisale ovaj receptor jer se pretpostavljalo da je odgovoran za snižavanje krvnog pritiska dejstvom kanabinoida. GPR55 je zaista aktiviran endogenim, biljnim i sintetičkim kanabinoidima. Međutim, GPR-55 nokaut miševi (generisani od strane Glakso istraživača) nisu demonstrirali promene u regulaciji krvnog pritiska nakon administracije derivata kanabidiola, abnormalnog kanabidiola.[6]

Signalna kaskada

GPR55 je spregnut sa G-proteinom G13 i aktivacija ovog receptora dovodi do stimulacije rhoA, cdc42 i rac1.[7]

Farmakologija

GPR55 se aktivira biljnim kanabinoidima Δ9-THC i kanabidiolom,[8] i endokanabinoidima: anandamidom, 2-AG, i noladin etrom u niskom nanomolarnom opsegu. Sintetički kanabinoid CP-55940 isto tako može da aktivira ovaj receptor[8], dok je strukturno različiti kanabinoidni ligand WIN 55,212-2 neaktivan.[6] Nedavna istraživanja sugestiraju da su lizofosfatidilinozitol i njegov 2-arahidonoil derivat mogući endogeni ligandi GPR55 receptora,[9][10][11] i da je ovaj receptor potencijalno može da bude biološki cilj za tretmane inflamacije i bola, kao što je to slučaj sa drugim kanabinoidnim receptorima.[12][13]

Reference

  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. PMID 17906678. 
  3. ↑ McHugh D, Hu SS, Rimmerman N, Juknat A, Vogil Z, Walker JM, Bradshaw HB (March 2010). „N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor”. BMC Neuroscience 11 (1): 44. DOI:10.1186/1471-2202-11-44. PMC 2865488. PMID 20346144. 
  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 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. 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. PMID 18263732. 
  8. ↑ 8,0 8,1 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. PMID 17876302. 
  9. ↑ 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. 
  10. ↑ 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. 
  11. ↑ 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. 
  12. ↑ 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. 
  13. ↑ Kress M, Kuner R (March 2009). „Mode of action of cannabinoids on nociceptive nerve endings”. Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale 196 (1): 79–88. DOI:10.1007/s00221-009-1762-0. PMID 19306092. 

Literatura

  • 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. PMC 139241. 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. PMC 528928. PMID 15489334. 
  • p
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Klasa A: Rodopsinu slični
α1 (A, B, D) • α2 (A, B, C) • β1 • β2 • β3
Adenozinski (A1, A2A, A2B, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
(svi osim 5-HT3) 5-HT1 (A, B, D, E, F) • 5-HT2 (A, B, C) • 5-HT (4, 5A, 6, 7)
Drugi
Acetilholin (M1, M2, M3, M4, M5) • Dopamin (D1, D2, D3, D4, D5) • Histamin (H1, H2, H3, H4) • Melatonin (1A, 1B, 1C) • TAAR (1, 2, 3, 5, 6, 8, 9)
Metaboliti i
signalni molekuli
CysLT (1, 2) • LTB4 (1, 2) • FPRL1 • OXE • Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) • Prostaciklin • Tromboksan
Drugi
Žučna kiselina • Kanabinoidni (CB1, CB2, GPR (18, 55, 119)) • EBI2 • Estrogen • Slobodna masna kiselina (1, 2, 3, 4) • Laktat  • Lizofosfatidna kiselina (1, 2, 3, 4, 5, 6)  • Lizofosfolipid (1, 2, 3, 4, 5, 6, 7, 8) • Niacin (1, 2) • Oksoglutarat • PAF • Sfingozin-1-fosfat (1, 2, 3, 4, 5) • Sukcinat
Peptid
B/W (1, 2) • FF (1, 2) • S • Y (1, 2, 4, 5) • Neuromedin (B, U (1, 2)) • Neurotenzin (1, 2)
Drugi
Anafilatoksin (C3a, C5a) • Angiotenzin (1, 2) • Apelin • Bombezin (BRS3, GRPR, NMBR) • Bradikinin (B1, B2) • Hemokin • Holecistokinin (A, B) • Endotelin (A, B) • Formil peptid (1, 2, 3) • FSH • Galanin (1, 2, 3) • GHB receptor • Gonadotropin-oslobađajući hormon (1, 2) • Grelin • Kispeptin • Luteinizirajući hormon/horiogonadotropin • MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) • Melanokortin (1, 2, 3, 4, 5) • MCHR (1, 2) • Motilin • Opioidni (δ, κ, μ, Nociceptin & ζ, ali ne σ) • Oreksin (1, 2) • Oksitocin • Prokineticin (1, 2) • Prolaktin-oslobađajući peptid • Relaksin (1, 2, 3, 4) • Somatostatin (1, 2, 3, 4, 5) • Tahikinin (1, 2, 3) • Tirotropin • Tirotropin-oslobađajući hormon • Urotenzin-II • Vazopresin (1A, 1B, 2)
Razno
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)
Drugi
Adrenomedulin • Mirisni • Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) • Proteazom-aktivirani (1, 2, 3, 4) • SREB (1, 2, 3)
Klasa B: Sekretinu slični
GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Drugi
Klasa C: Metabotropni
glutamat / feromon
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)
Drugi
Klasa F:
Frizzled / Zaglađeni
Uvojiti
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Zaglađeni
B trdu: peptidi (nrpl/grfl/cytl/horl), receptori (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd, signalni putevi (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)