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Article: Anti-arrhythmic Effect of κ -opioid Receptor Stimulation in the Perfused Rat Heart: Involvement of a cAMP-dependent Pathway

TitleAnti-arrhythmic Effect of κ -opioid Receptor Stimulation in the Perfused Rat Heart: Involvement of a cAMP-dependent Pathway
Authors
Keywordsκ -opioid receptor β -adrenoceptor
Arrhythmias
cAMP
[Ca2+]ioscillations
Issue Date1999
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yjmcc
Citation
Journal of Molecular and Cellular Cardiology, 1999, v. 31 n. 10, p. 1809-1819 How to Cite?
AbstractDuring myocardial ischaemia the β -adrenoceptor is activated, which contributes, at least partly, to cardiac arrhythmias via inducing [Ca2+]ioscillations. Since β -adrenoceptor is negatively modulated by the κ -opioid receptor in the heart, the present study attempted to determine if κ -opioid receptor stimulation modulates the arrhythmogenic action of β -adrenoceptor stimulation and to delineate the underlying mechanism. The effect of U50,488H, a selective κ -opioid agonist, on arrhythmias in the isolated perfused rat heart subjected to low flow and 10−6mol/l norepinephrine (NE) were determined. Low flow induced arrhythmias, which were potentiated by NE, but not by 10−6mol/l U50,488H. The arrhythmia-potentiating effect of NE was antagonized by 10−6mol/l propranolol, a β -adrenoceptor antagonist. U50,488H at 10−6mol/l also abolished the potentiation in arrhythmias by NE without affecting the arrhythmias induced by low flow. The anti-arrhythmic action of the κ -opioid receptor agonist was abolished by 10−6mol/l nor-binaltorphimine, a selective κ -opioid receptor antagonist, but not by 10−7mol/l calphostin C, an inhibitor of protein kinase C. Similarly, κ -opioid receptor stimulation with U50,488H also abolished the NE-induced [Ca2+]ioscillations which are believed to cause cardiac arrhythmias, in ventricular myocytes. To determine whether the inhibitory actions of U50,488H against the effects of β -adrenoceptor stimulation was via a cAMP-dependent or a cAMP-independent pathway, we determined the effects of U50,488H on NE-enhanced cAMP production and [Ca2+]ioscillations induced by either forskolin, an activator of adenylate cyclase, or Bay K-8644, a selective Full-size image (<1 K) -type Ca2+channel agonist, in the ventricular myocytes. We found that U50,488H abolished the effect of forskolin, but did not alter the effect of Bay K-8644, on [Ca2+]ioscillations in the ventricular myocyte. In addition, U50,488H also attenuated significantly the NE-induced elevation in cAMP in the heart. The observations suggest that κ -opioid receptor stimulation abolishes the effect of β -adrenoceptor stimulation on arrhythmias and [Ca2+]ioscillation via a cAMP-dependent pathway. The finding may be useful for the prevention and treatment of ischaemic heart diseases.
Persistent Identifierhttp://hdl.handle.net/10722/223779
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.522

 

DC FieldValueLanguage
dc.contributor.authorYu, XC-
dc.contributor.authorWang, HX-
dc.contributor.authorPei, JM-
dc.contributor.authorWong, PTM-
dc.date.accessioned2016-03-15T06:07:18Z-
dc.date.available2016-03-15T06:07:18Z-
dc.date.issued1999-
dc.identifier.citationJournal of Molecular and Cellular Cardiology, 1999, v. 31 n. 10, p. 1809-1819-
dc.identifier.issn0022-2828-
dc.identifier.urihttp://hdl.handle.net/10722/223779-
dc.description.abstractDuring myocardial ischaemia the β -adrenoceptor is activated, which contributes, at least partly, to cardiac arrhythmias via inducing [Ca2+]ioscillations. Since β -adrenoceptor is negatively modulated by the κ -opioid receptor in the heart, the present study attempted to determine if κ -opioid receptor stimulation modulates the arrhythmogenic action of β -adrenoceptor stimulation and to delineate the underlying mechanism. The effect of U50,488H, a selective κ -opioid agonist, on arrhythmias in the isolated perfused rat heart subjected to low flow and 10−6mol/l norepinephrine (NE) were determined. Low flow induced arrhythmias, which were potentiated by NE, but not by 10−6mol/l U50,488H. The arrhythmia-potentiating effect of NE was antagonized by 10−6mol/l propranolol, a β -adrenoceptor antagonist. U50,488H at 10−6mol/l also abolished the potentiation in arrhythmias by NE without affecting the arrhythmias induced by low flow. The anti-arrhythmic action of the κ -opioid receptor agonist was abolished by 10−6mol/l nor-binaltorphimine, a selective κ -opioid receptor antagonist, but not by 10−7mol/l calphostin C, an inhibitor of protein kinase C. Similarly, κ -opioid receptor stimulation with U50,488H also abolished the NE-induced [Ca2+]ioscillations which are believed to cause cardiac arrhythmias, in ventricular myocytes. To determine whether the inhibitory actions of U50,488H against the effects of β -adrenoceptor stimulation was via a cAMP-dependent or a cAMP-independent pathway, we determined the effects of U50,488H on NE-enhanced cAMP production and [Ca2+]ioscillations induced by either forskolin, an activator of adenylate cyclase, or Bay K-8644, a selective Full-size image (<1 K) -type Ca2+channel agonist, in the ventricular myocytes. We found that U50,488H abolished the effect of forskolin, but did not alter the effect of Bay K-8644, on [Ca2+]ioscillations in the ventricular myocyte. In addition, U50,488H also attenuated significantly the NE-induced elevation in cAMP in the heart. The observations suggest that κ -opioid receptor stimulation abolishes the effect of β -adrenoceptor stimulation on arrhythmias and [Ca2+]ioscillation via a cAMP-dependent pathway. The finding may be useful for the prevention and treatment of ischaemic heart diseases.-
dc.languageeng-
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yjmcc-
dc.relation.ispartofJournal of Molecular and Cellular Cardiology-
dc.rightsPosting accepted manuscript (postprint): © <year>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.subjectκ -opioid receptor β -adrenoceptor-
dc.subjectArrhythmias-
dc.subjectcAMP-
dc.subject[Ca2+]ioscillations-
dc.titleAnti-arrhythmic Effect of κ -opioid Receptor Stimulation in the Perfused Rat Heart: Involvement of a cAMP-dependent Pathway-
dc.typeArticle-
dc.identifier.emailWong, PTM: wongtakm@hkucc.hku.hk-
dc.identifier.hkuros54125-
dc.identifier.volume31-
dc.identifier.issue10-
dc.identifier.spage1809-
dc.identifier.epage1819-
dc.publisher.placeUnited Kingdom-

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