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Kapa opioidni receptor

С Википедије, слободне енциклопедије
(преусмерено са Κ-Opioid receptor)
Kapa opioidni receptor 1
Identifikatori
Simboli OPRK1; KOR; OPRK
Vanjski ID OMIM165196 MGI97439 HomoloGene20253 IUPHAR: κ GeneCards: OPRK1 Gene
Pregled RNK izražavanja
podaci
Ortolozi
Vrsta Čovek Miš
Entrez 4986 18387
Ensembl ENSG00000082556 ENSMUSG00000025905
UniProt P41145 Q14AL5
RefSeq (mRNA) NM_000912 NM_011011
RefSeq (protein) NP_000903 NP_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]

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]

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.

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]

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

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.

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

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