κ-opioid receptor
Template:PBB The κ-Opioid receptor is a type of opioid receptor which binds the peptide opioid dynorphin as the primary endogenous ligand.[1] κ receptors are widely distributed in the brain (hypothalamus, periaqueductal gray, and claustrum), spinal cord (substantia gelatinosa), and in pain neurons.[2][3]
Receptor subtypes
Based on receptor binding studies, three variants of the κ-opioid receptor designated κ1, κ2, and κ3 have been characterized.[4][5] However only one cDNA clone has been identified,[6] hence these receptor subtypes likely arise from interaction of one κ-opioid receptor protein with other membrane associated proteins.[7]
Function
It has long been understood that kappa-opioid receptor agonists are dysphoric[8] but dysphoria from kappa opioids has been shown to differ between sexes[9][10] More recent studies have shown the aversive properties in a variety of ways[11] and the kappa 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 hallucinogenic 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 effects are sought after. While salvinorin A is considered a hallucinogen, its effects are qualitatively different than those produced by the classical psychedelic hallucinogens such as LSD or mescaline.[12]
The involvement of the kappa-opioid receptor in stress response has been elucidated.[8]
Activation of the κ-opioid receptor appears to antagonize many of the effects of the μ opioid receptor.[13]
Kappa ligands are also known for their characteristic diuretic effects, due to their negative regulation of antidiuretic hormone (ADH).[14]
Kappa agonism is neuroprotective against hypoxia/ischemia; as such, kappa receptors may represent a novel therapeutic target.[15]
Signal transduction
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.[16][17][18] κ-Opioid receptors also couple to inward-rectifier potassium[19] and to N-type calcium ion channels.[20] 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.[21][22][23][24][25][26]
Ligands
The synthetic alkaloid ketazocine[27] and terpenoid natural product salvinorin A[12] 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.[28]
Agonists
- Asimadoline
- Butorphanol
- BRL-52537
- Cyclazocine
- Dynorphin (endogenous peptide ligand)
- Enadoline
- GR-89696 - selective for κ2 subtype
- HZ-2
- ICI-204,448 - peripherally selective
- Ketazocine
- LPK-26 - highly selective, Ki 0.64nM, 2-(3,4-Dichlorophenyl)-N-methyl-N-[(1S)-1-(2-isopropyl)-2-(1-(3-pyrrolinyl))ethyl]acetamide, CAS# 492451-07-7
- Menthol
- Nalbuphine
- Nalfurafine
- Pentazocine
- Salvinorin A
- 2-Methoxymethyl Salvinorin B[29] and its ethoxymethyl and fluoroethoxymethyl homologues[30][31]
- Spiradoline
- Tifluadom
- U-50488
- U-62066
- U-69593
Antagonists
Natural agonists
Mentha spp.
Found in numerous species of mint, (including peppermint, spearmint, and watermint), the naturally-occurring compound Menthol is a weak k-opioid receptor agonist[32] owing to its antinociceptive effects in rats. In addition, mints can desensitize a region through the activation of TRPM8 receptors (the 'cold'/menthol receptor).[33]
Salvia divinorum
The key compound in Salvia divinorum, Salvinorin A, is known as a non-toxic yet potent kappa-opioid agonist.[34][35]
Ibogaine
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 kappa opioid agonist[36] and this property may contribute to the drug's anti-addictive efficacy.
Role in Treatment of Drug Addiction
Kappa opioids have recently been investigated for their therapeutic potential in the treatment of addiction[37] and evidence points towards dynorphin, the endogenous kappa agonist, to be the body's natural addiction control mechanism.[38] Childhood stress/abuse is a well known predictor of drug abuse and is reflected in alterations of the mu and kappa opioid systems.[39] In experimental "addiction" models the Kappa-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 Kappa-opioid receptors are required for stress-induced reinstatement of cocaine seeking.[40][41]
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.[42] In addition to low NAcc D2 binding,[43][44] 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 kappa agonist produced an opposite effect causing an increase in D2 receptors in the NAcc.[45]
Additionally, while cocaine overdose victims showed a large increase in kappa receptors (doubled) in the NAcc,[46] kappa opioid agonist administration is shown to be effective in decreasing cocaine seeking and self-administration.[47] Furthermore, while cocaine abuse is associated with lowered prolactin response,[48] kappa opioid activation causes a release in prolactin,[49] a hormone known for its important role in learning, neuronal plasticity and myelination.[50]
It has also been reported that the dynorphin-Kappa 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.[51][52] These effects are likely caused by stress-induced drug craving that requires activation of the dynorphin/kappa 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[53] The rewarding properties of drug are altered, and it is clear kappa-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 Kappa opioid receptors is likely due to multiple signaling mechanisms. The effects of kappa-opioid agonism on dopamine systems are well documented, and recent work also implicates the mitogen-activated protein kinase cascade and pCREB in Kappa-opioid dependent behaviors. [24][54]
Though cocaine abuse is a frequently used model of addiction, kappa opioids have very marked effects on all types of addiction including alcohol and opiate abuse.[11] Not only are genetic differences in dynorphin receptor expression a marker for alcohol dependence, but a single dose of a kappa opioid antagonist markedly increased alcohol consumption in lab animals.[55] There are numerous studies which reflect a reduction in self-administration of alcohol,[56] and heroin dependence has also been shown to be effectively treated with kappa agonism by reducing the immediate rewarding effects[57] and by causing the curative effect of up-regulation of mu-opioid receptors[58] which have been down-regulated during opioid abuse.
The anti-rewarding properties of kappa opioid agonists are mediated through both long-term and short-term effects. The immediate effect of kappa agonism leads to reduction of dopamine release in the NAcc during self administration of cocaine[59] and over the long term up-regulates receptors which have been down-regulated during substance abuse such as mu-opioid and D2 (dopamine) receptors. These receptors modulate the release of other neurochemicals such as serotonin in the case of mu-opioids 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 kappa opioid agonism (30 minutes or greater) have been linked to kappa opioid dependent stress-induced potentiation and reinstatement of drug seeking. It is hypothesized that these behaviors are mediated by kappa opioid-dependent modulation of dopamine, serotonin, or norepinephrine and/or via activation of downstream signal transduction pathways.
Interactions
Kappa Opioid receptor has been shown to interact with Sodium-hydrogen antiporter 3 regulator 1[60][61] and Ubiquitin C.[62]
References
- ^ 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.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Fine, Perry G. (2004). "Chapter 2: The Endogenous Opioid System". A Clinical Guide to Opioid Analgesia. McGraw Hill.
{{cite book}}
: Cite has empty unknown parameters:|accessmonth=
,|accessyear=
, and|month=
(help); External link in
(help); Unknown parameter|chapterurl=
|chapterurl=
ignored (|chapter-url=
suggested) (help); Unknown parameter|coauthors=
ignored (|author=
suggested) (help) - ^ 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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Jordan BA, Devi LA (1999). "G-protein-coupled receptor heterodimerization modulates receptor function". Nature. 399 (6737): 697–700. doi:10.1038/21441. PMID 10385123.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ a b 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 2612708. PMID 18184783.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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 (2006). "Association of the kappa-opioid system with alcohol dependence". Mol. Psychiatry. 11 (11): 1016–24. doi:10.1038/sj.mp.4001882. PMID 16924269.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) Cite error: The named reference "pmid16924269" was defined multiple times with different content (see the help page). - ^ 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. PMID 12192085.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) Cite error: The named reference "pmid12192085" was defined multiple times with different content (see the help page). - ^ 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.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ 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.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ 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.
{{cite journal}}
: Explicit use of et al. in:|author=
(help); Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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 2504523. PMID 10646507.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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 1400585. PMID 15944153.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Bruchas MR, Macey TA, Lowe JD, Chavkin C (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b 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. PMID 18766023.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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 2096775. PMID 17702750.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ 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. PMID 6251477.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Holtzman SG (1985). "Drug discrimination studies". Drug Alcohol Depend. 14 (3–4): 263–82. doi:10.1016/0376-8716(85)90061-4. PMID 2859972.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Wang Y, Chen Y, Xu W, Lee DY, Ma Z, Rawls SM, Cowan A, Liu-Chen LY (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Munro TA, Duncan KK, Xu W, Wang Y, Liu-Chen LY, Carlezon WA, Cohen BM, Béguin C (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Baker LE, Panos JJ, Killinger BA, Peet MM, Bell LM, Haliw LA, Walker SL (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Galeotti N, Di Cesare Mannelli L, Mazzanti G, Bartolini A, Ghelardini C (2002). "Menthol: a natural analgesic compound". Neurosci. Lett. 322 (3): 145–8. doi:10.1016/S0304-3940(01)02527-7. PMID 11897159.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Werkheiser JL, Rawls SM, Cowan A (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Butelman ER, Mandau M, Tidgewell K, Prisinzano TE, Yuferov V, Kreek MJ (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Chavkin C, Sud S, Jin W, Stewart J, Zjawiony JK, Siebert DJ, Toth BA, Hufeisen SJ, Roth BL (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Hasebe K, Kawai K, Suzuki T, Kawamura K, Tanaka T, Narita M, Nagase H, Suzuki T (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Frankel PS, Alburges ME, Bush L, Hanson GR, Kish SJ (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. PMID 18538358.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Michaels CC, Holtzman SG (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Beardsley PM, Howard JL, Shelton KL, Carroll FI (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Redila VA, Chavkin C (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. PMID 18575850.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Blum K, Braverman ER, Holder JM, Lubar JF, Monastra VJ, Miller D, Lubar JO, Chen TJ, Comings DE (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Stefański R, Ziółkowska B, Kuśmider M, Mierzejewski P, Wyszogrodzka E, Kołomańska P, Dziedzicka-Wasylewska M, Przewłocki R, Kostowski W (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Moore RJ, Vinsant SL, Nader MA, Porrino LJ, Friedman DP (1998). "Effect of cocaine self-administration on dopamine D2 receptors in rhesus monkeys". Synapse (New York, N.Y.). 30 (1): 88–96. PMID 9704885.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ D'Addario C, Di Benedetto M, Izenwasser S, Candeletti S, Romualdi P (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Mash DC, Staley JK (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Schenk S, Partridge B, Shippenberg TS (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Patkar AA, Mannelli P, Hill KP, Peindl K, Pae CU, Lee TH (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Butelman ER, Kreek MJ (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Gregg C, Shikar V, Larsen P, Mak G, Chojnacki A, Yong VW, Weiss S (2007). "White matter plasticity and enhanced remyelination in the maternal CNS". The Journal of neuroscience : the official journal of the Society for Neuroscience. 27 (8): 1812–23. doi:10.1523/JNEUROSCI.4441-06.2007. PMID 17314279.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ McLaughlin JP, Marton-Popovici M, Chavkin C. (2003). "Kappa opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses". The Journal of neuroscience : the official journal of the Society for Neuroscience. 23 (13): 5674–83. doi:10.1111/j.1749-6632.1999.tb09286.x. PMID 12843270.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Mash, DEBORAH C. (2006). "Social defeat stress-induced behavioral responses are mediated by the endogenous kappa opioid system". Neuropsychopharmacology. 31 (4): 787–94. doi:10.1111/j.1749-6632.1999.tb09286.x. PMID 16123746.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Koob GF (2008). "A role for brain stress systems in addiction". Neuron. 59 (1): 11–34. doi:10.1016/j.neuron.2008.06.012. PMID 18614026.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ 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, 11614–11623.
- ^ Mitchell JM, Liang MT, Fields HL (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Walker BM, Koob GF (2008). "Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence". Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 33 (3): 643–52. doi:10.1038/sj.npp.1301438. PMID 17473837.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Xi ZX, Fuller SA, Stein EA (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Narita M, Khotib J, Suzuki M, Ozaki S, Yajima Y, Suzuki T (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Maisonneuve IM, Archer S, Glick SD (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.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Huang, Peng (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. 279 (24). United States: 25002–9. doi:10.1074/jbc.M313366200. ISSN 0021-9258. PMID 15070904.
{{cite journal}}
: Check date values in:|year=
(help); Cite has empty unknown parameters:|laydate=
,|laysource=
, and|laysummary=
(help); Unknown parameter|coauthors=
ignored (|author=
suggested) (help); Unknown parameter|month=
ignored (help); Unknown parameter|quotes=
ignored (help)CS1 maint: unflagged free DOI (link) CS1 maint: year (link) - ^ Li, Jian-Guo (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. 277 (30). United States: 27545–52. doi:10.1074/jbc.M200058200. ISSN 0021-9258. PMID 12004055.
{{cite journal}}
: Check date values in:|year=
(help); Cite has empty unknown parameters:|laydate=
,|laysource=
, and|laysummary=
(help); Unknown parameter|coauthors=
ignored (|author=
suggested) (help); Unknown parameter|month=
ignored (help); Unknown parameter|quotes=
ignored (help)CS1 maint: unflagged free DOI (link) CS1 maint: year (link) - ^ Li, Jian-Guo (2008). "Agonist-promoted Lys63-linked polyubiquitination of the human kappa-opioid receptor is involved in receptor down-regulation". Mol. Pharmacol. 73 (4). United States: 1319–30. doi:10.1124/mol.107.042846. PMID 18212250.
{{cite journal}}
: Check date values in:|year=
(help); Cite has empty unknown parameters:|laydate=
,|laysource=
, and|laysummary=
(help); Unknown parameter|coauthors=
ignored (|author=
suggested) (help); Unknown parameter|month=
ignored (help); Unknown parameter|quotes=
ignored (help)CS1 maint: year (link)
External links
- "Opioid Receptors: κ". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
{{cite web}}
: Cite has empty unknown parameter:|coauthors=
(help) - kappa+Opioid+Receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)