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Article: Inhibition of [3H]-U69593 binding and the cardiac effects of U50,488H by calcium channel blockers in the rat heart

TitleInhibition of [3H]-U69593 binding and the cardiac effects of U50,488H by calcium channel blockers in the rat heart
Authors
KeywordsCa2+ channel blocker
Rat isolated heart
Arrhythmias
kappa-opioid receptor
Receptor binding assay
Issue Date1997
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjp
Citation
British Journal of Pharmacology, 1997, v. 120 n. 5, p. 827-832 How to Cite?
Abstract1. The calcium channel blockers (CCBs), nifedipine, nicardipine, diltiazem and verapamil, were used to displace the binding of [3H]-U69593 ((5a, 7a,8b)-(+)-N-methyl-N-(7-[1-pyrrolidinyl]-1-oxaspiro[4,5] dec-8-yl)-benzeneacetamide), a specific kappa-opioid agonist, in the rat cardiac sarcolemma. The CCBs competed with the binding of [3H]-U69593 (4 nM) in a dose-dependent manner. The displacing potency of verapamil was 55 times greater than that of nifedipine. 2. The effects of two CCBs, verapamil and nifedipine, on the arrhythmogenic action of kappa-receptor stimulation by a specific kappa-receptor agonist, U50,488H (trans-(+/-(-3),4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] cyclohexyl) benzeacetamide methanesulphonate), were also studied in the rat isolated perfused heart. U50,488H 80-800 nmol dose-dependently induced arrhythmias, which were completely abolished by a selective kappa-receptor antagonist, nor-BNI (nor-binaltorphimine, 17,17'-(dicyclopropylmethyl)-6,6',7,7'-6,6'-imino-7,7'-binorphinan -3,4',14, 14'-tetrol), at 100 nmol. The arrhythmogenic effect was also attenuated by both verapamil and nifedipine in a dose-dependent manner. The ED50 values for verapamil and nifedipine were 2.75 and 63.7 nmol, respectively. The antiarrhythmic potencies of these two CCBs were correlated to their displacing potencies and inversely related to their well known potencies in inhibiting transmembrane Ca2+ influx in the cardiac muscle. 3. Measurement of [Ca2+]i in the absence of free extracellular Ca2+ by a spectrofluorometric method, with fura-2 as Ca2+ indicator, showed that U50,488H 5 x 10(-5) M slowly increased [Ca2+]i in single ventricular myocytes and this effect was abolished by pretreatment with nor-BNI (5 microM), or ryanodine (5 microM). Verapamil 1 and 10 microM abolished the effect of U50,488H in 37.5% (3 out of 8) and 100% (12 out of 12) of the cells studied, respectively. On the other hand, nifedipine 10 and 100 microM had no effect at all. Neither verapamil nor nifedipine exerted any significant effect on the caffeine-induced Ca2+ transient. 4. The observations suggest that CCBs may inhibit the actions of kappa-receptor stimulation at the level of the kappa-receptor.
Persistent Identifierhttp://hdl.handle.net/10722/49290
ISSN
2023 Impact Factor: 6.8
2023 SCImago Journal Rankings: 2.119
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, WMen_HK
dc.contributor.authorWang, HXen_HK
dc.contributor.authorXia, Qen_HK
dc.contributor.authorWong, TMen_HK
dc.date.accessioned2008-06-12T06:38:38Z-
dc.date.available2008-06-12T06:38:38Z-
dc.date.issued1997en_HK
dc.identifier.citationBritish Journal of Pharmacology, 1997, v. 120 n. 5, p. 827-832en_HK
dc.identifier.issn0007-1188en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49290-
dc.description.abstract1. The calcium channel blockers (CCBs), nifedipine, nicardipine, diltiazem and verapamil, were used to displace the binding of [3H]-U69593 ((5a, 7a,8b)-(+)-N-methyl-N-(7-[1-pyrrolidinyl]-1-oxaspiro[4,5] dec-8-yl)-benzeneacetamide), a specific kappa-opioid agonist, in the rat cardiac sarcolemma. The CCBs competed with the binding of [3H]-U69593 (4 nM) in a dose-dependent manner. The displacing potency of verapamil was 55 times greater than that of nifedipine. 2. The effects of two CCBs, verapamil and nifedipine, on the arrhythmogenic action of kappa-receptor stimulation by a specific kappa-receptor agonist, U50,488H (trans-(+/-(-3),4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] cyclohexyl) benzeacetamide methanesulphonate), were also studied in the rat isolated perfused heart. U50,488H 80-800 nmol dose-dependently induced arrhythmias, which were completely abolished by a selective kappa-receptor antagonist, nor-BNI (nor-binaltorphimine, 17,17'-(dicyclopropylmethyl)-6,6',7,7'-6,6'-imino-7,7'-binorphinan -3,4',14, 14'-tetrol), at 100 nmol. The arrhythmogenic effect was also attenuated by both verapamil and nifedipine in a dose-dependent manner. The ED50 values for verapamil and nifedipine were 2.75 and 63.7 nmol, respectively. The antiarrhythmic potencies of these two CCBs were correlated to their displacing potencies and inversely related to their well known potencies in inhibiting transmembrane Ca2+ influx in the cardiac muscle. 3. Measurement of [Ca2+]i in the absence of free extracellular Ca2+ by a spectrofluorometric method, with fura-2 as Ca2+ indicator, showed that U50,488H 5 x 10(-5) M slowly increased [Ca2+]i in single ventricular myocytes and this effect was abolished by pretreatment with nor-BNI (5 microM), or ryanodine (5 microM). Verapamil 1 and 10 microM abolished the effect of U50,488H in 37.5% (3 out of 8) and 100% (12 out of 12) of the cells studied, respectively. On the other hand, nifedipine 10 and 100 microM had no effect at all. Neither verapamil nor nifedipine exerted any significant effect on the caffeine-induced Ca2+ transient. 4. The observations suggest that CCBs may inhibit the actions of kappa-receptor stimulation at the level of the kappa-receptor.en_HK
dc.format.extent418 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjpen_HK
dc.relation.ispartofBritish Journal of Pharmacology-
dc.subjectCa2+ channel blockeren_HK
dc.subjectRat isolated hearten_HK
dc.subjectArrhythmiasen_HK
dc.subjectkappa-opioid receptoren_HK
dc.subjectReceptor binding assayen_HK
dc.titleInhibition of [3H]-U69593 binding and the cardiac effects of U50,488H by calcium channel blockers in the rat hearten_HK
dc.typeArticleen_HK
dc.identifier.emailWong, TM: wongtakm@hkucc.hku.hken_HK
dc.description.naturelink_to_OA_fulltexten_HK
dc.identifier.doi10.1038/sj.bjp.0700985en_HK
dc.identifier.pmid9138688-
dc.identifier.pmcidPMC1564545-
dc.identifier.scopuseid_2-s2.0-0030615235-
dc.identifier.hkuros25198-
dc.identifier.volume120-
dc.identifier.issue5-
dc.identifier.spage827-
dc.identifier.epage832-
dc.identifier.isiWOS:A1997WL16100015-
dc.identifier.issnl0007-1188-

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