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Article: Effects of κ-opioid receptor stimulation in the heart and the involvement of protein kinase C

TitleEffects of κ-opioid receptor stimulation in the heart and the involvement of protein kinase C
Authors
KeywordsU50,488H
k-opioid receptor
Protein kinase C
Cyclic AMP
Intracellular Ca2+
Issue Date1998
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjp
Citation
British Journal of Pharmacology, 1998, v. 124 n. 3, p. 600-606 How to Cite?
Abstract1. The role of protein kinase C (PKC) in mediating the action of kappa-receptor stimulation on intracellular Ca2+ and cyclic AMP production was determined by studying the effects of trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] cyclohexyl) benzeneacetamide methanesulphonate (U50,488H), a selective kappa-receptor agonist, and phorbol 12-myristate 13-acetate (PMA), a PKC agonist, on the electrically-induced [Ca2+]i transient and forskolin-stimulated cyclic AMP accumulation in the presence and absence of a PKC antagonist, staurosporine or chelerythrine, in the single rat ventricular myocyte. 2. U50,488H at 2.5-40 microM decreased both the electrically-induced [Ca2+]i transient and forskolin-stimulated cyclic AMP accumulation dose-dependently, effects which PMA mimicked. The effects of the kappa-agonist, that were blocked by a selective kappa-antagonist, nor-binaltorphimine, were significantly antagonized by the PKC antagonists, staurosporine and/or chelerythrine. The results indicate that PKC mediates the actions of kappa-receptor stimulation. 3. To determine whether the action of PKC was at the sarcoplasmic reticulum (SR) or not, the [Ca2+]i transient induced by caffeine, that depletes the SR of Ca2+, was used as an indicator of Ca2+ content in the SR. The caffeine-induced [Ca2+]i transient was significantly reduced by U50,488H at 20 microM. This effect of U50,488H on caffeine-induced [Ca2+]i transient was significantly attenuated by 1 microM chelerythrine, indicating that the action of PKC involves mobilization of Ca2+ from the SR. When the increase in IP3 production in response to K-receptor stimulation with U50,488H in the ventricular myocyte was determined, the effect of U50,488H was the same in the presence and absence of staurosporine, suggesting that the effect of PKC activation subsequent to kappa-receptor stimulation does not involve IP3. The observations suggest that PKC may act directly at the SR. 4. In conclusion, the present study has provided evidence for the first time that PKC may be involved in the action of kappa-receptor stimulation on Ca2+ in the SR and cyclic AMP production, both of which play an essential role in Ca2+ homeostasis in the heart.
Persistent Identifierhttp://hdl.handle.net/10722/49296
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
PubMed Central ID
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DC FieldValueLanguage
dc.contributor.authorBian, JSen_HK
dc.contributor.authorWang, HXen_HK
dc.contributor.authorZhang, WMen_HK
dc.contributor.authorWong, TMen_HK
dc.date.accessioned2008-06-12T06:38:46Z-
dc.date.available2008-06-12T06:38:46Z-
dc.date.issued1998en_HK
dc.identifier.citationBritish Journal of Pharmacology, 1998, v. 124 n. 3, p. 600-606en_HK
dc.identifier.issn0007-1188en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49296-
dc.description.abstract1. The role of protein kinase C (PKC) in mediating the action of kappa-receptor stimulation on intracellular Ca2+ and cyclic AMP production was determined by studying the effects of trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] cyclohexyl) benzeneacetamide methanesulphonate (U50,488H), a selective kappa-receptor agonist, and phorbol 12-myristate 13-acetate (PMA), a PKC agonist, on the electrically-induced [Ca2+]i transient and forskolin-stimulated cyclic AMP accumulation in the presence and absence of a PKC antagonist, staurosporine or chelerythrine, in the single rat ventricular myocyte. 2. U50,488H at 2.5-40 microM decreased both the electrically-induced [Ca2+]i transient and forskolin-stimulated cyclic AMP accumulation dose-dependently, effects which PMA mimicked. The effects of the kappa-agonist, that were blocked by a selective kappa-antagonist, nor-binaltorphimine, were significantly antagonized by the PKC antagonists, staurosporine and/or chelerythrine. The results indicate that PKC mediates the actions of kappa-receptor stimulation. 3. To determine whether the action of PKC was at the sarcoplasmic reticulum (SR) or not, the [Ca2+]i transient induced by caffeine, that depletes the SR of Ca2+, was used as an indicator of Ca2+ content in the SR. The caffeine-induced [Ca2+]i transient was significantly reduced by U50,488H at 20 microM. This effect of U50,488H on caffeine-induced [Ca2+]i transient was significantly attenuated by 1 microM chelerythrine, indicating that the action of PKC involves mobilization of Ca2+ from the SR. When the increase in IP3 production in response to K-receptor stimulation with U50,488H in the ventricular myocyte was determined, the effect of U50,488H was the same in the presence and absence of staurosporine, suggesting that the effect of PKC activation subsequent to kappa-receptor stimulation does not involve IP3. The observations suggest that PKC may act directly at the SR. 4. In conclusion, the present study has provided evidence for the first time that PKC may be involved in the action of kappa-receptor stimulation on Ca2+ in the SR and cyclic AMP production, both of which play an essential role in Ca2+ homeostasis in the heart.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.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectU50,488Hen_HK
dc.subjectk-opioid receptoren_HK
dc.subjectProtein kinase Cen_HK
dc.subjectCyclic AMPen_HK
dc.subjectIntracellular Ca2+en_HK
dc.titleEffects of κ-opioid receptor stimulation in the heart and the involvement of protein kinase Cen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0007-1188&volume=124&issue=3&spage=600&epage=606&date=1998&atitle=Effects+of+κ-opioid+receptor+stimulation+in+the+heart+and+the+involvement+of+protein+kinase+Cen_HK
dc.identifier.emailWong, TM: wongtakm@hkucc.hku.hken_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1038/sj.bjp.0701857en_HK
dc.identifier.pmid9647487-
dc.identifier.pmcidPMC1565412-
dc.identifier.scopuseid_2-s2.0-0031779909-
dc.identifier.isiWOS:000073924900026-

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