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Kapa opioidni receptor

Izvor: Wikipedija
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Kapa opioidni receptor 1
Identifikatori
SimboliOPRK1; KOR; OPRK
Vanjski IDOMIM165196 MGI97439 HomoloGene20253 IUPHAR: κ GeneCards: OPRK1 Gene
Pregled RNK izražavanja
podaci
Ortolozi
VrstaČovekMiš
Entrez498618387
EnsemblENSG00000082556ENSMUSG00000025905
UniProtP41145Q14AL5
RefSeq (mRNA)NM_000912NM_011011
RefSeq (protein)NP_000903NP_035141
Lokacija (UCSC)Chr 8:
54.3 - 54.33 Mb
Chr 1:
5.58 - 5.59 Mb
PubMed pretraga[1][2]

κ-opioidni receptor (KOR) je tip opioidnog receptora koji vezuje opioidne peptide dinorfine kao primarne endogene ligande.[1] κ-opioidni receptor je široko rasprostranjen u mozgu (hipotalamus, centralna siva masa, i claustrum), kičmenoj moždini (substantia gelatinosa), i u neuronima bola.[2][3]

Tipovi

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Na osnovu istraživanja receptorskog vezivanja, tri varijante κ-opioidnog receptora se karakterisane: κ1, κ2, i κ3.[4][5] Međutim, samo jedan cDNK klon je identifikovan,[6] i stoga su ovi receptorski tipovi verovatno posledica interakcija sa drugum membranskim proteinima.[7]

Funkcija

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Dugo vremena je poznato da su agonisti κ-opioidnog receptora disforični.[8] Međutim, takođe je pokazano je da disforija uzrokovana agonistima κ-opioidnog receptora zavisna od pola osobe.[9][10] Nedavna istraživanja ukazuju na niz drugih nuspojava.[11] κ-opioidni receptor se smatra integralnom neurohemijskom komponentom adikcije i remisije.

Prenos signala

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Aktivacija κ-opioidnog receptora agonistima je vezana sa G proteinimam Gi/G0, koji naknadno povišavaju aktivnost fosfodiesteraze. Ona razlaže cAMP, proizvodeći inhibitorni efekat u neuronima.[12][13][14] κ-opioidni receptori se takođe sprežu sa unutrašnje ispravljajućim kalijumskim[15] i N-tip kalcijumskim jonskim kanalima.[16] Pokazano je da agonistom indukovana stimulacija κ-opioidnog receptora, poput drugih G-protein spregnutih receptora, može da dovede do aktivacije mitogenom-aktiviranih proteinskih kinaza (MAPK). To obuhvata ekstracelularnim signalom regulisanu kinazu, p38 MAP kinazu, i c-Jun N-terminalnu kinazu.[17][18][19][20][21][22]

Ligandi

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Sintetički alkaloid ketazocin[23] i terpenoidni prirodni proizvod salvinorin A[24] su potentni i selektivni agonisti κ-opioidnog receptora. Ovaj receptor takođe posreduje dejstvo halucinogenih nuspojava opioida poput pentazocina.[25]

Prirodni agonist

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Menta

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Glavni članak: mentol

Nađeno u brojnim vrstama minta (pepermint, Mentha spicata, i Mentha aquatica), prirodno jedinjenje mentol je slab agonist k-opioidnog receptora[29]. Mint isto tako može da desenzitiviše region putem aktivacije TRPM8 receptora ('hladnoća'/mentol receptor).[30]

Salvia divinorum

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Glavni članak: Salvia divinorum

Ključno jedinjenje u Salvia divinorum, Salvinorin A, je poznato kao netoksični i potentni agonist κ-opioidnog receptora.[31][32]

Ibogain

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Glavni članak: ibogain

Ibogain se koristi se za lečenje adikcije u pojedinim zemljama. On je postao ikona menadžmenta adikcije u nekim krugovima. Uprkos toga što ne izaziva zavisnost, ibogain se tretira kao kontrolisana supstanca u SAD-u, i stoga je njegovo posedovanje ilegalno. Ibogain je agonist κ-opioidnog receptora[33] i ta osobina može da doprinese njegovoj antizavisničkoj efikasnosti.

Interakcije

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Za κ-opioidni receptor je pokazano da interaguje sa natrijum-vodonik antiporter 3 regulatorom 1[34][35] i ubikvitinom C.[36]

Povezano

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Reference

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  2. Fine, Perry G.; Russell K. Portenoy (2004). „Chapter 2: The Endogenous Opioid System”. A Clinical Guide to Opioid Analgesia. McGraw Hill. Arhivirano iz originala na datum 2011-07-19. 
  3. Mansour A, Fox CA, Akil H, Watson SJ (January 1995). „Opioid-receptor mRNA expression in the rat CNS: anatomical and functional implications”. Trends Neurosci. 18 (1): 22-9. DOI:10.1016/0166-2236(95)93946-U. PMID 7535487. 
  4. de Costa BR, Rothman RB, Bykov V, Jacobson AE, Rice KC (February 1989). „Selective and enantiospecific acylation of kappa opioid receptors by (1S,2S)-trans-2-isothiocyanato-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexy l] benzeneacetamide. Demonstration of kappa receptor heterogeneity”. J. Med. Chem. 32 (2): 281-3. DOI:10.1021/jm00122a001. PMID 2536435. 
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  21. Kam AY, Chan AS, Wong YH (July 2004). „Kappa-opioid receptor signals through Src and focal adhesion kinase to stimulate c-Jun N-terminal kinases in transfected COS-7 cells and human monocytic THP-1 cells”. J. Pharmacol. Exp. Ther. 310 (1): 301-10. DOI:10.1124/jpet.104.065078. PMID 14996948. 
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  34. Huang, Peng; Steplock Deborah, Weinman Edward J, Hall Randy A, Ding Zhe, Li Jianguo, Wang Yulin, Liu-Chen Lee-Yuan (June 2004). „kappa Opioid receptor interacts with Na(+)/H(+)-exchanger regulatory factor-1/Ezrin-radixin-moesin-binding phosphoprotein-50 (NHERF-1/EBP50) to stimulate Na(+)/H(+) exchange independent of G(i)/G(o) proteins”. J. Biol. Chem. (United States) 279 (24): 25002-9. DOI:10.1074/jbc.M313366200. ISSN 0021-9258. PMID 15070904. 
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  36. Li, Jian-Guo; Haines Dale S, Liu-Chen Lee-Yuan (April 2008). „Agonist-promoted Lys63-linked polyubiquitination of the human kappa-opioid receptor is involved in receptor down-regulation”. Mol. Pharmacol. (United States) 73 (4): 1319-30. DOI:10.1124/mol.107.042846. PMID 18212250. 

Literatura

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Spoljašnje veze

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