Kapa opioidni receptor

Из Википедије, слободне енциклопедије
Kapa opioidni receptor 1
Identifikatori
Simboli OPRK1; KOR; OPRK
Vanjski ID OMIM165196 MGI97439 HomoloGene20253 IUPHAR: κ GeneCards: OPRK1 Gene
Pregled RNK izražavanja
PBB GE OPRK1 207553 at tn.png
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]

Tipovi[уреди]

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[уреди]

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[уреди]

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[уреди]

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[уреди]

Menta[уреди]

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[уреди]

Glavni članak: Salvia divinorum

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

Ibogain[уреди]

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[уреди]

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

Vidi još[уреди]

Референце[уреди]

  1. James IF, Chavkin C, Goldstein A (1982). „Selectivity of dynorphin for kappa opioid receptors”. Life Sci. 31 (12-13): 1331—4. doi:10.1016/0024-3205(82)90374-5. PMID 6128656. 
  2. Fine, Perry G.; Russell K. Portenoy (2004). „Chapter 2: The Endogenous Opioid System” (PDF). A Clinical Guide to Opioid Analgesia. McGraw Hill. 
  3. Mansour A, Fox CA, Akil H, Watson SJ (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 (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. 
  5. Rothman RB, France CP, Bykov V, De Costa BR, Jacobson AE, Woods JH, Rice KC (1989). „Pharmacological activities of optically pure enantiomers of the kappa opioid agonist, U50,488, and its cis diastereomer: evidence for three kappa receptor subtypes”. Eur. J. Pharmacol. 167 (3): 345—53. doi:10.1016/0014-2999(89)90443-3. PMID 2553442. 
  6. Mansson E, Bare L, Yang D (1994). „Isolation of a human kappa opioid receptor cDNA from placenta”. Biochem. Biophys. Res. Commun. 202 (3): 1431—7. doi:10.1006/bbrc.1994.2091. PMID 8060324. 
  7. Jordan BA, Devi LA (1999). „G-protein-coupled receptor heterodimerization modulates receptor function”. Nature. 399 (6737): 697—700. doi:10.1038/21441. PMID 10385123. 
  8. Land BB, Bruchas MR, Lemos JC, Xu M, Melief EJ, Chavkin C (2008). „The dysphoric component of stress is encoded by activation of the dynorphin kappa-opioid system”. J. Neurosci. 28 (2): 407—14. doi:10.1523/JNEUROSCI.4458-07.2008. PMC 2612708Слободан приступ. PMID 18184783. 
  9. Lomas LM, Barrett AC, Terner JM, Lysle DT, Picker MJ (2007). „Sex differences in the potency of kappa opioids and mixed-action opioids administered systemically and at the site of inflammation against capsaicin-induced hyperalgesia in rats”. Psychopharmacology (Berl.). 191 (2): 273—85. doi:10.1007/s00213-006-0663-1. PMID 17225166. 
  10. Sershen H, Hashim A, Lajtha A (1998). „Gender differences in kappa-opioid modulation of cocaine-induced behavior and NMDA-evoked dopamine release”. Brain Res. 801 (1-2): 67—71. doi:10.1016/S0006-8993(98)00546-0. PMID 9729284. 
  11. Xuei X, Dick D, Flury-Wetherill L, Tian HJ, Agrawal A, Bierut L, Goate A, Bucholz K, Schuckit M, Nurnberger J, Tischfield J, Kuperman S, Porjesz B, Begleiter H, Foroud T, Edenberg HJ (2006). „Association of the kappa-opioid system with alcohol dependence”. Mol. Psychiatry. 11 (11): 1016—24. doi:10.1038/sj.mp.4001882. PMID 16924269. 
  12. Lawrence DM, Bidlack JM (1993). „The kappa opioid receptor expressed on the mouse R1.1 thymoma cell line is coupled to adenylyl cyclase through a pertussis toxin-sensitive guanine nucleotide-binding regulatory protein”. J. Pharmacol. Exp. Ther. 266 (3): 1678—83. PMID 8103800. 
  13. Konkoy CS, Childers SR (1993). „Relationship between kappa 1 opioid receptor binding and inhibition of adenylyl cyclase in guinea pig brain membranes”. Biochem. Pharmacol. 45 (1): 207—16. doi:10.1016/0006-2952(93)90394-C. PMID 8381004. 
  14. Schoffelmeer AN; Rice KC; Jacobson AE; et al. (1988). „Mu-, delta- and kappa-opioid receptor-mediated inhibition of neurotransmitter release and adenylate cyclase activity in rat brain slices: studies with fentanyl isothiocyanate”. Eur. J. Pharmacol. 154 (2): 169—78. doi:10.1016/0014-2999(88)90094-5. PMID 2906610. 
  15. Henry DJ, Grandy DK, Lester HA, Davidson N, Chavkin C (1995). „Kappa-opioid receptors couple to inwardly rectifying potassium channels when coexpressed by Xenopus oocytes”. Mol. Pharmacol. 47 (3): 551—7. PMID 7700253. 
  16. Tallent M, Dichter MA, Bell GI, Reisine T (1994). „The cloned kappa opioid receptor couples to an N-type calcium current in undifferentiated PC-12 cells”. Neuroscience. 63 (4): 1033—40. doi:10.1016/0306-4522(94)90570-3. PMID 7700508. 
  17. Bohn LM, Belcheva MM, Coscia CJ (2000). „Mitogenic signaling via endogenous kappa-opioid receptors in C6 glioma cells: evidence for the involvement of protein kinase C and the mitogen-activated protein kinase signaling cascade.”. J Neurochem. 74 (2): 564—73. doi:10.1046/j.1471-4159.2000.740564.x. PMC 2504523Слободан приступ. PMID 10646507. 
  18. Belcheva MM, Clark AL, Haas PD, Serna JS, Hahn JW, Kiss A, Coscia CJ (2005). „Mu and kappa opioid receptors activate ERK/MAPK via different protein kinase C isoforms and secondary messengers in astrocytes”. J. Biol. Chem. 280 (30): 27662—9. doi:10.1074/jbc.M502593200. PMC 1400585Слободан приступ. PMID 15944153. 
  19. Bruchas MR, Macey TA, Lowe JD, Chavkin C (2006). „Kappa opioid receptor activation of, pp. 38 MAPK is GRK3- and arrestin-dependent in neurons and astrocytes”. J. Biol. Chem. 281 (26): 18081—9. doi:10.1074/jbc.M513640200. PMC 2096730Слободан приступ. PMID 16648139. 
  20. Bruchas MR, Xu M, Chavkin C (2008). „Repeated swim stress induces kappa opioid-mediated activation of extracellular signal-regulated kinase 1/2”. Neuroreport. 19 (14): 1417—22. doi:10.1097/WNR.0b013e32830dd655. PMC 2641011Слободан приступ. PMID 18766023. 
  21. Kam AY, Chan AS, Wong YH (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. 
  22. Bruchas MR, Yang T, Schreiber S, Defino M, Kwan SC, Li S, Chavkin C (2007). „Long-acting kappa opioid antagonists disrupt receptor signaling and produce noncompetitive effects by activating c-Jun N-terminal kinase”. J. Biol. Chem. 282 (41): 29803—11. doi:10.1074/jbc.M705540200. PMC 2096775Слободан приступ. PMID 17702750. 
  23. Pasternak GW (1980). „Multiple opiate receptors: [3H]ethylketocyclazocine receptor binding and ketocyclazocine analgesia”. Proc. Natl. Acad. Sci. U.S.A. 77 (6): 3691—4. doi:10.1073/pnas.77.6.3691. PMC 349684Слободан приступ. PMID 6251477. 
  24. Roth BL; Baner K; Westkaemper R; et al. (2002). „Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist”. Proc. Natl. Acad. Sci. U.S.A. 99 (18): 11934—9. doi:10.1073/pnas.182234399. PMC 129372Слободан приступ. PMID 12192085. 
  25. Holtzman SG (1985). „Drug discrimination studies”. Drug Alcohol Depend. 14 (3-4): 263—82. doi:10.1016/0376-8716(85)90061-4. PMID 2859972. 
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  33. Glick SD, Maisonneuve IS (1998). „Mechanisms of antiaddictive actions of ibogaine”. Annals of the New York Academy of Sciences. 844: 214—26. doi:10.1111/j.1749-6632.1998.tb08237.x. PMID 9668680. 
  34. Huang, Peng; Steplock Deborah, Weinman Edward J, Hall Randy A, Ding Zhe, Li Jianguo, Wang Yulin, Liu-Chen Lee-Yuan (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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Литература[уреди]

Spoljašnje veze[уреди]