GPR55 — разлика између измена

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-{GPR55}- je spregnut sa [[G-protein]]om [[G12/G13 alfa podjedinice|-{G<sub>13</sub>}-]] i aktivacija ovog receptora dovodi do stimulacije -{[[rhoA]], [[cdc42]]}- i -{[[rac1]]}-.<ref name="pmid18263732">{{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 | pmc = 2268199 }}</ref>
-{GPR55}- je spregnut sa [[G-protein]]om [[G12/G13 alfa podjedinice|-{G<sub>13</sub>}-]] i aktivacija ovog receptora dovodi do stimulacije -{[[rhoA]], [[cdc42]]}- i -{[[rac1]]}-.<ref name="pmid18263732">{{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 | pmc = 2268199 }}</ref>

== Farmakologija ==

-{GPR55}- se aktivira biljnim kanabinoidima Δ<sup>9</sup>--{THC}- i kanabidiolom,<ref name="pmid17876302">{{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 | pmc = 2095107 }}</ref> i [[endokanabinoid]]ima [[anandamid]]om, -{[[2-AG]]}-, [[noladin etar]]om u niskom nanomolarnom opsegu. Sintetički kanabinoid -{[[CP-55940]]}- takođe može da aktivira ovaj receptor<ref name="pmid17876302"/>, dok je strukturno različiti kanabinoidni ligand -{[[WIN 55,212-2]]}- neaktivan.<ref name="pmid17704827"/> Nedavna istraživanja sugestiraju da su lizofosfatidilinozitol i njegov 2-arahidonoil derivat mogući endogeni ligandi -{GPR55}- receptora,<ref name="pmid17765871">{{cite journal | author = Oka S, Nakajima K, Yamashita A, Kishimoto S, Sugiura T | title = Identification of GPR55 as a lysophosphatidylinositol receptor | journal = Biochemical and Biophysical Research Communications | volume = 362 | issue = 4 | pages = 928–34 | year = 2007 | month = November | pmid = 17765871 | doi = 10.1016/j.bbrc.2007.08.078 | url = | issn = }}</ref><ref name="pmid18757503">{{cite journal | author = Henstridge CM, Balenga NA, Ford LA, Ross RA, Waldhoer M, Irving AJ | title = The GPR55 ligand L-alpha-lysophosphatidylinositol promotes RhoA-dependent Ca2+ signaling and NFAT activation | journal = The FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology | volume = 23 | issue = 1 | pages = 183–93 | year = 2009 | month = January | pmid = 18757503 | doi = 10.1096/fj.08-108670 | url = | issn = }}</ref><ref name="pmid18845565">{{cite journal | author = Oka S, Toshida T, Maruyama K, Nakajima K, Yamashita A, Sugiura T | title = 2-Arachidonoyl-sn-glycero-3-phosphoinositol: a possible natural ligand for GPR55 | journal = Journal of Biochemistry | volume = 145 | issue = 1 | pages = 13–20 | year = 2009 | month = January | pmid = 18845565 | doi = 10.1093/jb/mvn136 | url = | issn = }}</ref> 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.<ref name="pmid18502582">{{cite journal | author = 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 | title = The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain | journal = Pain | volume = 139 | issue = 1 | pages = 225–36 | year = 2008 | month = September | pmid = 18502582 | doi = 10.1016/j.pain.2008.04.006 | url = | issn = }}</ref><ref name="pmid19306092">{{cite journal | author = Kress M, Kuner R | title = Mode of action of cannabinoids on nociceptive nerve endings | journal = Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale | volume = 196| issue = 1| pages = 79–88| year = 2009 | month = March | pmid = 19306092 | doi = 10.1007/s00221-009-1762-0 | url = | issn = }}</ref>


==Literatura==
==Literatura==

Верзија на датум 5. април 2011. у 22:06

G protein-spregnuti receptor 55
Identifikatori
Simboli GPR55;
Vanjski ID OMIM604107 MGI2685064 HomoloGene36184 IUPHAR: GPR55 GeneCards: GPR55 Gene
Ortolozi
Vrsta Čovek Miš
Entrez 9290 227326
Ensembl ENSG00000135898 ENSMUSG00000049608
UniProt Q9Y2T6 Q14BV9
RefSeq (mRNA) NM_005683 NM_001033290
RefSeq (protein) NP_005674 NP_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 Glakso Smit Klajn i Astra Zeneka 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, noladin etarom u niskom nanomolarnom opsegu. Sintetički kanabinoid CP-55940 takođe 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]

Literatura

  1. ^ „Entrez Gene: GPR55 G protein-coupled receptor 55”. 
  2. ^ Brown AJ. (2007). „Novel cannabinoid receptors.”. Br J Pharmacol. 152 (5): 567—575. PMC 2190013Слободан приступ. PMID 17906678. doi:10.1038/sj.bjp.0707481. 
  3. ^ McHugh D, Hu SS, Rimmerman N, Juknat A, Vogil Z, Walker JM, Bradshaw HB (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. PMC 2865488Слободан приступ. PMID 20346144. doi:10.1186/1471-2202-11-44.  Непознати параметар |month= игнорисан (помоћ)
  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. PMID 9931487. doi:10.1016/S0169-328X(98)00277-0. 
  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. PMID 16318877. doi:10.1016/j.tips.2005.11.003. 
  6. ^ а б 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. PMC 2190033Слободан приступ. PMID 17704827. doi:10.1038/sj.bjp.0707419. 
  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. PMC 2268199Слободан приступ. PMID 18263732. doi:10.1073/pnas.0711278105. 
  8. ^ а б 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. PMC 2095107Слободан приступ. PMID 17876302. doi:10.1038/sj.bjp.0707460. 
  9. ^ Oka S, Nakajima K, Yamashita A, Kishimoto S, Sugiura T (2007). „Identification of GPR55 as a lysophosphatidylinositol receptor”. Biochemical and Biophysical Research Communications. 362 (4): 928—34. PMID 17765871. doi:10.1016/j.bbrc.2007.08.078.  Непознати параметар |month= игнорисан (помоћ)
  10. ^ Henstridge CM, Balenga NA, Ford LA, Ross RA, Waldhoer M, Irving AJ (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. PMID 18757503. doi:10.1096/fj.08-108670.  Непознати параметар |month= игнорисан (помоћ)
  11. ^ Oka S, Toshida T, Maruyama K, Nakajima K, Yamashita A, Sugiura T (2009). „2-Arachidonoyl-sn-glycero-3-phosphoinositol: a possible natural ligand for GPR55”. Journal of Biochemistry. 145 (1): 13—20. PMID 18845565. doi:10.1093/jb/mvn136.  Непознати параметар |month= игнорисан (помоћ)
  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 (2008). „The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain”. Pain. 139 (1): 225—36. PMID 18502582. doi:10.1016/j.pain.2008.04.006.  Непознати параметар |month= игнорисан (помоћ)
  13. ^ Kress M, Kuner R (2009). „Mode of action of cannabinoids on nociceptive nerve endings”. Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 196 (1): 79—88. PMID 19306092. doi:10.1007/s00221-009-1762-0.  Непознати параметар |month= игнорисан (помоћ)

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