kappa Opioid receptor
Opioid receptor, kappa 1
Rendering based on PDB .
Available structures PDB , Identifiers Symbols External IDs IUPHAR: GeneCards: Gene Ontology Molecular function •
Cellular component •
Biological process •
Sources: Amigo / QuickGO RNA expression pattern Orthologs Species Human Mouse Entrez Ensembl UniProt RefSeq (mRNA) RefSeq (protein) Location (UCSC) PubMed search
The κ-opioid receptor (KOR) is a protein that in humans is encoded by the OPRK1 gene. The κ-opioid receptor is one of five related receptors that bind opium-like compounds in the brain and are responsible for mediating the effects of these compounds. These effects include altering the perception of pain, consciousness, motor control, and mood.
The κ-opioid receptor is a type of opioid receptor that binds the opioid peptide dynorphin as the primary endogenous ligand. In addition to dynorphin, a variety of natural alkaloids and synthetic ligands bind to the receptor. The κ-opioid receptor may provide a natural addiction control mechanism, and consequently selective agonists of this receptor may have therapeutic potential in the treatment of addiction.
Based on receptor binding studies, three variants of the κ-opioid receptor designated κ1, κ2, and κ3 have been characterized. However only one cDNA clone has been identified, hence these receptor subtypes likely arise from interaction of one κ-opioid receptor protein with other membrane associated proteins.
It has long been understood that κ-opioid receptor agonists are dysphoric but dysphoria from κ-opioid receptor agonists has been shown to differ between the sexes. More recent studies have shown the aversive properties in a variety of ways and the κ-opioid receptor has been strongly implicated as an integral neurochemical component of addiction and the remission thereof.
It is now widely accepted that κ-opioid receptor (partial) agonists have dissociative and deliriant effects, as exemplified by salvinorin A. These effects are generally undesirable in medicinal drugs and could have had frightening or disturbing effects in the tested humans. It is thought that the hallucinogenic effects of drugs such as butorphanol, nalbuphine, and pentazocine serve to limit their opiate abuse potential. In the case of salvinorin A, a structurally novel neoclerodane diterpene κ-opioid receptor agonist, these hallucinogenic, more specifically deliriant and dissociative, effects are sought after, even though the experience is often considered dysphoric by the user. While salvinorin A is considered a hallucinogen, it is not a psychedelic, and its effects are qualitatively different than those produced by the classical psychedelic hallucinogens such as LSD or mescaline.
κ-Opioid receptor activation by agonists is coupled to the G protein Gi/G0, which subsequently increases phosphodiesterase activity. Phosphodiesterases break down cAMP, producing an inhibitory effect in neurons. κ-Opioid receptors also couple to inward-rectifier potassium and to N-type calcium ion channels. Recent studies have also demonstrated that agonist-induced stimulation of the κ-Opioid receptor, like other G-protein coupled receptors, can result in the activation of mitogen-activated protein kinases (MAPK). These include extracellular signal-regulated kinase, p38 MAP kinases, and c-Jun N-terminal kinases.
The synthetic alkaloid ketazocine and terpenoid natural product salvinorin A are potent and selective κ-opioid receptor agonists. The κ-opioid receptor also mediates the action of the hallucinogenic side effects of opioids such as pentazocine.
- Dynorphin (endogenous peptide ligand)
- GR-89696 - selective for κ2 subtype
- ICI-204,448 - peripherally selective
- LPK-26 - highly selective
- Oxycodone (disputed)
- Salvinorin A
- 2-Methoxymethyl Salvinorin B and its ethoxymethyl and fluoroethoxymethyl homologues
Found in numerous species of mint, (including peppermint, spearmint, and watermint), the naturally-occurring compound Menthol is a weak k-opioid receptor agonist owing to its antinociceptive effects in rats. In addition, mints can desensitize a region through the activation of TRPM8 receptors (the 'cold'/menthol receptor).
Used for the treatment of addiction in limited countries, ibogaine has become an icon of addiction management among certain underground circles. Despite its lack of addictive properties, ibogaine is listed as a Schedule I compound in the US, hence it is considered illegal to possess under any circumstances. Ibogaine is also a κ-opioid agonist and this property may contribute to the drug's anti-addictive efficacy.
Role in treatment of drug addiction
κ-Opioid agonists have recently been investigated for their therapeutic potential in the treatment of addiction and evidence points towards dynorphin, the endogenous κ-opioid agonist, to be the body's natural addiction control mechanism. Childhood stress/abuse is a well known predictor of drug abuse and is reflected in alterations of the μ- and κ-opioid systems. In experimental "addiction" models the κ-opioid receptor has also been shown to influence stress-induced relapse to drug seeking behavior. For the drug dependent individual, risk of relapse is a major obstacle to becoming drug free. Recent reports demonstrated that κ-opioid receptors are required for stress-induced reinstatement of cocaine seeking.
One area of the brain most strongly associated with addiction is the nucleus accumbens (NAcc) and striatum while other structures that project to and from the NAcc also play a critical role. Though many other changes occur, addiction is often characterized by the reduction of dopamine D2 receptors in the NAcc. In addition to low NAcc D2 binding, cocaine is also known to produce a variety of changes to the primate brain such as increases prodynorphin mRNA in caudate putamen (striatum) and decreases of the same in the hypothalamus while the administration of a κ-opioid agonist produced an opposite effect causing an increase in D2 receptors in the NAcc.
Additionally, while cocaine overdose victims showed a large increase in κ-opioid receptors (doubled) in the NAcc, κ-opioid agonist administration is shown to be effective in decreasing cocaine seeking and self-administration. Furthermore, while cocaine abuse is associated with lowered prolactin response, κ-opioid activation causes a release in prolactin, a hormone known for its important role in learning, neuronal plasticity and myelination.
It has also been reported that the κ-opioid system is critical for stress-induced drug-seeking. In animal models, stress has been demonstrated to potentiate cocaine reward behavior in a kappa opioid-dependent manner. These effects are likely caused by stress-induced drug craving that requires activation of the κ-opioid system. Although seemingly paradoxical, it is well known that drug taking results in a change from homeostasis to allostasis. It has been suggested that withdrawal-induced dysphoria or stress-induced dysphoria may act as a driving force by which the individual seeks alleviation via drug taking The rewarding properties of drug are altered, and it is clear κ-opioid activation following stress modulates the valence of drug to increase its rewarding properties and cause potentiation of reward behavior, or reinstatement to drug seeking. The stress-induced activation of κ-opioid receptors is likely due to multiple signaling mechanisms. The effects of κ-opioid agonism on dopamine systems are well documented, and recent work also implicates the mitogen-activated protein kinase cascade and pCREB in κ-opioid dependent behaviors. 
Though cocaine abuse is a frequently used model of addiction, κ-opioid agonists have very marked effects on all types of addiction including alcohol and opiate abuse. Not only are genetic differences in dynorphin receptor expression a marker for alcohol dependence but a single dose of a κ-opioid antagonist markedly increased alcohol consumption in lab animals. There are numerous studies that reflect a reduction in self-administration of alcohol, and heroin dependence has also been shown to be effectively treated with κ-opioid agonism by reducing the immediate rewarding effects and by causing the curative effect of up-regulation of μ-opioid receptors that have been down-regulated during opioid abuse.
The anti-rewarding properties of κ-opioid agonists are mediated through both long-term and short-term effects. The immediate effect of κ-opioid agonism leads to reduction of dopamine release in the NAcc during self administration of cocaine and over the long term up-regulates receptors that have been down-regulated during substance abuse such as μ-opioid and D2 receptors. These receptors modulate the release of other neurochemicals such as serotonin in the case of μ-opioid receptor agonists and acetylcholine in the case of D2. These changes can account for the physical and psychological remission of the pathology of addiction. The longer effects of κ-opioid agonism (30 minutes or greater) have been linked to κ-opioid receptor-dependent stress-induced potentiation and reinstatement of drug seeking. It is hypothesized that these behaviors are mediated by κ-opioid-dependent modulation of dopamine, serotonin, or norepinephrine and/or via activation of downstream signal transduction pathways.
- ^ 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.
- ^ Fine, Perry G.; Russell K. Portenoy (2004). "Chapter 2: The Endogenous Opioid System". A Clinical Guide to Opioid Analgesia. McGraw Hill. http://www.stoppain.org/pcd/_pdf/OpioidChapter2.pdf.
- ^ 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. http://linkinghub.elsevier.com/retrieve/pii/016622369593946U.
- ^ 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.
- ^ Rothman RB, France CP, Bykov V, De Costa BR, Jacobson AE, Woods JH, Rice KC (August 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.
- ^ Mansson E, Bare L, Yang D (August 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.
- ^ Jordan BA, Devi LA (June 1999). "G-protein-coupled receptor heterodimerization modulates receptor function". Nature 399 (6737): 697–700. doi:10.1038/21441. PMC 3125690. PMID 10385123. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3125690.
- ^ a b Land BB, Bruchas MR, Lemos JC, Xu M, Melief EJ, Chavkin C (January 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 2612708. PMID 18184783. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2612708.
- ^ Lomas LM, Barrett AC, Terner JM, Lysle DT, Picker MJ (April 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.
- ^ Sershen H, Hashim A, Lajtha A (August 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.
- ^ a b 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 (November 2006). "Association of the kappa-opioid system with alcohol dependence". Mol. Psychiatry 11 (11): 1016–24. doi:10.1038/sj.mp.4001882. PMID 16924269.
- ^ a b Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC, Steinberg S, Ernsberger P, Rothman RB (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 129372. PMID 12192085. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=129372.
- ^ Pan ZZ (1998). "mu-Opposing actions of the kappa-opioid receptor". Trends Pharmacol. Sci. 19 (3): 94–8. doi:10.1016/S0165-6147(98)01169-9. PMID 9584625.
- ^ Yamada K, Imai M, Yoshida S (1989). "Mechanism of diuretic action of U-62,066E, a kappa opioid receptor agonist". Eur. J. Pharmacol. 160 (2): 229–37. doi:10.1016/0014-2999(89)90495-0. PMID 2547626.
- ^ Zeynalov E, Nemoto M, Hurn PD, Koehler RC, Bhardwaj A (2006). "Neuroprotective effect of selective kappa opioid receptor agonist is gender specific and linked to reduced neuronal nitric oxide". J. Cereb. Blood Flow Metab. 26 (3): 414–20. doi:10.1038/sj.jcbfm.9600196. PMID 16049424.
- ^ Lawrence DM, Bidlack JM (September 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. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8103800.
- ^ Konkoy CS, Childers SR (January 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. http://linkinghub.elsevier.com/retrieve/pii/0006-2952(93)90394-C.
- ^ Schoffelmeer AN, Rice KC, Jacobson AE et al. (September 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. http://linkinghub.elsevier.com/retrieve/pii/0014-2999(88)90094-5.
- ^ Henry DJ, Grandy DK, Lester HA, Davidson N, Chavkin C (March 1995). "Kappa-opioid receptors couple to inwardly rectifying potassium channels when coexpressed by Xenopus oocytes". Mol. Pharmacol. 47 (3): 551–7. PMID 7700253. http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7700253.
- ^ Tallent M, Dichter MA, Bell GI, Reisine T (December 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. http://linkinghub.elsevier.com/retrieve/pii/0306-4522(94)90570-3.
- ^ Bohn LM, Belcheva MM, Coscia CJ (February 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 2504523. PMID 10646507. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2504523.
- ^ Belcheva MM, Clark AL, Haas PD, Serna JS, Hahn JW, Kiss A, Coscia CJ (July 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 1400585. PMID 15944153. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1400585.
- ^ Bruchas MR, Macey TA, Lowe JD, Chavkin C (June 2006). "Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin-dependent in neurons and astrocytes". J. Biol. Chem. 281 (26): 18081–9. doi:10.1074/jbc.M513640200. PMC 2096730. PMID 16648139. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2096730.
- ^ a b Bruchas MR, Xu M, Chavkin C (September 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 2641011. PMID 18766023. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2641011.
- ^ 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.
- ^ Bruchas MR, Yang T, Schreiber S, Defino M, Kwan SC, Li S, Chavkin C (October 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 2096775. PMID 17702750. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2096775.
- ^ Pasternak GW (June 1980). "Multiple opiate receptors: [3Hethylketocyclazocine receptor binding and ketocyclazocine analgesia"]. Proc. Natl. Acad. Sci. U.S.A. 77 (6): 3691–4. doi:10.1073/pnas.77.6.3691. PMC 349684. PMID 6251477. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=349684.
- ^ Holtzman SG (February 1985). "Drug discrimination studies". Drug Alcohol Depend 14 (3–4): 263–82. doi:10.1016/0376-8716(85)90061-4. PMID 2859972.
- ^ Wang Y, Chen Y, Xu W, Lee DY, Ma Z, Rawls SM, Cowan A, Liu-Chen LY (March 2008). "2-Methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A". The Journal of Pharmacology and Experimental Therapeutics 324 (3): 1073–83. doi:10.1124/jpet.107.132142. PMC 2519046. PMID 18089845. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2519046.
- ^ Munro TA, Duncan KK, Xu W, Wang Y, Liu-Chen LY, Carlezon WA, Cohen BM, Béguin C (February 2008). "Standard protecting groups create potent and selective kappa opioids: salvinorin B alkoxymethyl ethers". Bioorganic & Medicinal Chemistry 16 (3): 1279–86. doi:10.1016/j.bmc.2007.10.067. PMC 2568987. PMID 17981041. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2568987.
- ^ Baker LE, Panos JJ, Killinger BA, Peet MM, Bell LM, Haliw LA, Walker SL (April 2009). "Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats". Psychopharmacology 203 (2): 203–11. doi:10.1007/s00213-008-1458-3. PMID 19153716.
- ^ Galeotti N, Di Cesare Mannelli L, Mazzanti G, Bartolini A, Ghelardini C (April 2002). "Menthol: a natural analgesic compound". Neurosci. Lett. 322 (3): 145–8. doi:10.1016/S0304-3940(01)02527-7. PMID 11897159.
- ^ Werkheiser JL, Rawls SM, Cowan A (October 2006). "Mu and kappa opioid receptor agonists antagonize icilin-induced wet-dog shaking in rats". Eur. J. Pharmacol. 547 (1–3): 101–5. doi:10.1016/j.ejphar.2006.07.026. PMID 16945367.
- ^ Butelman ER, Mandau M, Tidgewell K, Prisinzano TE, Yuferov V, Kreek MJ (January 2007). "Effects of salvinorin A, a kappa-opioid hallucinogen, on a neuroendocrine biomarker assay in nonhuman primates with high kappa-receptor homology to humans". The Journal of pharmacology and experimental therapeutics 320 (1): 300–6. doi:10.1124/jpet.106.112417. PMID 17060493.
- ^ Chavkin C, Sud S, Jin W, Stewart J, Zjawiony JK, Siebert DJ, Toth BA, Hufeisen SJ, Roth BL (March 2004). "Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations". The Journal of pharmacology and experimental therapeutics 308 (3): 1197–203. doi:10.1124/jpet.103.059394. PMID 14718611.
- ^ Glick SD, Maisonneuve IS (May 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.
- ^ Hasebe K, Kawai K, Suzuki T, Kawamura K, Tanaka T, Narita M, Nagase H, Suzuki T (October 2004). "Possible pharmacotherapy of the opioid kappa receptor agonist for drug dependence". Annals of the New York Academy of Sciences 1025: 404–13. doi:10.1196/annals.1316.050. PMID 15542743.
- ^ Frankel PS, Alburges ME, Bush L, Hanson GR, Kish SJ (July 2008). "Striatal and ventral pallidum dynorphin concentrations are markedly increased in human chronic cocaine users". Neuropharmacology 55 (1): 41–6. doi:10.1016/j.neuropharm.2008.04.019. PMC 2577569. PMID 18538358. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2577569.
- ^ Michaels CC, Holtzman SG (April 2008). "Early postnatal stress alters place conditioning to both mu- and kappa-opioid agonists". The Journal of pharmacology and experimental therapeutics 325 (1): 313–8. doi:10.1124/jpet.107.129908. PMID 18203949.
- ^ Beardsley PM, Howard JL, Shelton KL, Carroll FI (November 2005). "Differential effects of the novel kappa opioid receptor antagonist, JDTic, on reinstatement of cocaine-seeking induced by footshock stressors vs cocaine primes and its antidepressant-like effects in rats". Psychopharmacology (Berl.) 183 (1): 118–26. doi:10.1007/s00213-005-0167-4. PMID 16184376.
- ^ Redila VA, Chavkin C (September 2008). "Stress-induced reinstatement of cocaine seeking is mediated by the kappa opioid system". Psychopharmacology (Berl.) 200 (1): 59–70. doi:10.1007/s00213-008-1122-y. PMC 2680147. PMID 18575850. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2680147.
- ^ Blum K, Braverman ER, Holder JM, Lubar JF, Monastra VJ, Miller D, Lubar JO, Chen TJ, Comings DE (November 2000). "Reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors". Journal of psychoactive drugs 32 Suppl: i–iv, 1–112. PMID 11280926.
- ^ Stefański R, Ziółkowska B, Kuśmider M, Mierzejewski P, Wyszogrodzka E, Kołomańska P, Dziedzicka-Wasylewska M, Przewłocki R, Kostowski W (July 2007). "Active versus passive cocaine administration: differences in the neuroadaptive changes in the brain dopaminergic system". Brain research 1157: 1–10. doi:10.1016/j.brainres.2007.04.074. PMID 17544385.
- ^ Moore RJ, Vinsant SL, Nader MA, Porrino LJ, Friedman DP (September 1998). "Effect of cocaine self-administration on dopamine D2 receptors in rhesus monkeys". Synapse 30 (1): 88–96. doi:10.1002/(SICI)1098-2396(199809)30:1<88::AID-SYN11>3.0.CO;2-L. PMID 9704885.
- ^ D'Addario C, Di Benedetto M, Izenwasser S, Candeletti S, Romualdi P (January 2007). "Role of serotonin in the regulation of the dynorphinergic system by a kappa-opioid agonist and cocaine treatment in rat CNS". Neuroscience 144 (1): 157–64. doi:10.1016/j.neuroscience.2006.09.008. PMID 17055175.
- ^ Mash DC, Staley JK (June 1999). "D3 dopamine and kappa opioid receptor alterations in human brain of cocaine-overdose victims". Annals of the New York Academy of Sciences 877: 507–22. doi:10.1111/j.1749-6632.1999.tb09286.x. PMID 10415668.
- ^ Schenk S, Partridge B, Shippenberg TS (June 1999). "U69593, a kappa-opioid agonist, decreases cocaine self-administration and decreases cocaine-produced drug-seeking". Psychopharmacology 144 (4): 339–46. doi:10.1007/s002130051016. PMID 10435406.
- ^ Patkar AA, Mannelli P, Hill KP, Peindl K, Pae CU, Lee TH (August 2006). "Relationship of prolactin response to meta-chlorophenylpiperazine with severity of drug use in cocaine dependence". Human psychopharmacology 21 (6): 367–75. doi:10.1002/hup.780. PMID 16915581.
- ^ Butelman ER, Kreek MJ (July 2001). "kappa-Opioid receptor agonist-induced prolactin release in primates is blocked by dopamine D(2)-like receptor agonists". European journal of pharmacology 423 (2–3): 243–9. doi:10.1016/S0014-2999(01)01121-9. PMID 11448491.
- ^ Gregg C, Shikar V, Larsen P, Mak G, Chojnacki A, Yong VW, Weiss S (February 2007). "White matter plasticity and enhanced remyelination in the maternal CNS". Journal of Neuroscience 27 (8): 1812–23. doi:10.1523/JNEUROSCI.4441-06.2007. PMID 17314279.
- ^ McLaughlin JP, Marton-Popovici M, Chavkin C. (July 2003). "Kappa opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses". Journal of Neuroscience 23 (13): 5674–83. PMC 2104777. PMID 12843270. http://www.jneurosci.org/cgi/reprint/23/13/5674.
- ^ Mash, DEBORAH C.; Li, S; Valdez, J; Chavkin, TA; Chavkin, C (June 2006). "Social defeat stress-induced behavioral responses are mediated by the endogenous kappa opioid system". Neuropsychopharmacology 31 (4): 787–94. doi:10.1038/sj.npp.1300872. PMC 2096774. PMID 16123746. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2096774.
- ^ Koob GF (July 2008). "A role for brain stress systems in addiction". Neuron 59 (1): 11–34. doi:10.1016/j.neuron.2008.06.012. PMC 2748830. PMID 18614026. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2748830.
- ^ Bruchas M. R., Land B. B., Aita M., Xu M., Barot S. K., Li S., Chavkin C. (2007). "Stress-induced p38 mitogen-activated protein kinase activation mediates -opioid-dependent dysphoria". J Neurosci 27 (43): 11614–23. doi:10.1523/JNEUROSCI.3769-07.2007. PMC 2481272. PMID 17959804. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2481272.
- ^ Mitchell JM, Liang MT, Fields HL (November 2005). "A single injection of the kappa opioid antagonist norbinaltorphimine increases ethanol consumption in rats". Psychopharmacology 182 (3): 384–92. doi:10.1007/s00213-005-0067-7. PMID 16001119.
- ^ Walker BM, Koob GF (February 2008). "Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence". Neuropsychopharmacology 33 (3): 643–52. doi:10.1038/sj.npp.1301438. PMC 2739278. PMID 17473837. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2739278.
- ^ Xi ZX, Fuller SA, Stein EA (January 1998). "Dopamine release in the nucleus accumbens during heroin self-administration is modulated by kappa opioid receptors: an in vivo fast-cyclic voltammetry study". The Journal of pharmacology and experimental therapeutics 284 (1): 151–61. PMID 9435173. http://jpet.aspetjournals.org/cgi/content/abstract/284/1/151.
- ^ Narita M, Khotib J, Suzuki M, Ozaki S, Yajima Y, Suzuki T (June 2003). "Heterologous mu-opioid receptor adaptation by repeated stimulation of kappa-opioid receptor: up-regulation of G-protein activation and antinociception". Journal of neurochemistry 85 (5): 1171–9. doi:10.1046/j.1471-4159.2003.01754.x. PMID 12753076.
- ^ Maisonneuve IM, Archer S, Glick SD (November 1994). "U50,488, a kappa opioid receptor agonist, attenuates cocaine-induced increases in extracellular dopamine in the nucleus accumbens of rats". Neuroscience letters 181 (1–2): 57–60. doi:10.1016/0304-3940(94)90559-2. PMID 7898771.
- ^ Huang, Peng; Steplock Deborah, Weinman Edward J, Hall Randy A, Ding Zhe, Li Jianguo, Wang Yulin, Liu-Chen Lee-Yuan (Jun. 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.
- ^ Li, Jian-Guo; Chen Chongguang, Liu-Chen Lee-Yuan (Jul. 2002). "Ezrin-radixin-moesin-binding phosphoprotein-50/Na+/H+ exchanger regulatory factor (EBP50/NHERF) blocks U50,488H-induced down-regulation of the human kappa opioid receptor by enhancing its recycling rate". J. Biol. Chem. (United States) 277 (30): 27545–52. doi:10.1074/jbc.M200058200. ISSN 0021-9258. PMID 12004055.
- ^ Li, Jian-Guo; Haines Dale S, Liu-Chen Lee-Yuan (Apr. 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.
- "Opioid Receptors: κ". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2409.
- MeSH kappa+Opioid+Receptor
Neuropeptide receptors G protein-coupled receptorOtherOther neuropeptide receptors Type I cytokine receptor Enzyme-linked receptor Other
Wikimedia Foundation. 2010.
Look at other dictionaries:
Kappa Opioid receptor — The κ Opioid receptor is a type of opioid receptor which binds the peptide opioid dynorphin as the primary endogenous ligand.cite journal | author = James IF, Chavkin C, Goldstein A | title = Selectivity of dynorphin for kappa opioid receptors |… … Wikipedia
Opioid receptor — Opioid receptors are a group of G protein coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are 40% identical to somatostatin… … Wikipedia
delta Opioid receptor — Opioid receptor, delta 1 Rendering based on PDB 1OZC … Wikipedia
mu Opioid receptor — Opioid receptor, mu 1 Identifiers Symbols OPRM1; KIAA0403; LMOR; MOR; MOR1; OPRM External IDs … Wikipedia
Delta Opioid receptor — The δ opioid receptors, also known as delta opioid receptor or simply delta receptor, abbreviated DOR, is an opioid receptor that has enkephalins as their endogenous ligands.cite journal | author = Quock RM, Burkey TH, Varga E, Hosohata Y,… … Wikipedia
Opioid — Endogenous opioid peptides Skeletal molecular images Adrenorphin Amidorphin Casomorphin … Wikipedia
Opioid antagonist — An opioid antagonist is a receptor antagonist that acts on opioid receptors. Naloxone and naltrexone are commonly used opioid antagonist drugs which are competitive antagonists that bind to the opioid receptors with higher affinity than agonists… … Wikipedia
Opioid — Schlafmohn, Papaver somniferum, aus dessen Milch Opioide gewonnen werden Opioid (von gr. ὄπιον [ˈɔpiɔn] und … Deutsch Wikipedia
Nociceptin receptor — Opiate receptor like 1 Identifiers Symbols OPRL1; KOR 3; MGC34578; NOCIR; OOR; ORL1 External IDs … Wikipedia
Neuropeptide FF receptor — 1 Identifiers Symbol NPFFR1 Alt. symbols GPR147 Entrez 64106 … Wikipedia