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Article: Role of protein kinase C-epsilon in the development of κ-opioid receptor tolerance to U50,488H in rat ventricular myocytes

TitleRole of protein kinase C-epsilon in the development of κ-opioid receptor tolerance to U50,488H in rat ventricular myocytes
Authors
KeywordsTolerance
Protein kinase C-epsilon
κ-opioid receptor
Ventricular myocytes
Issue Date2002
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjp
Citation
British Journal of Pharmacology, 2002, v. 135 n. 7, p. 1675-1784 How to Cite?
AbstractThe role of protein kinase C-epsilon (PKC-epsilon) in the development of kappa-opioid receptor (kappa-OR) tolerance to the effects of trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl) (U50,488H), the selective agonist of kappa-OR, was determined in rat ventricular myocytes. Incubation of ventricular myocytes with 1 microM U50,488H for 24 h significantly attenuated the inhibitory effects of 30 microM U50,488H on the electrically-induced [Ca(2+)](i) transient and forskolin-stimulated cyclic AMP accumulation, indicating the development of tolerance to the kappa-OR agonist. Chronic treatment of ventricular myocytes with U50,488H also induced translocation of PKC-epsilon to the particulate fraction. On the other hand, administration of 30 microM U50,488H for 10 min induced translocation of PKC-alpha to the particulate fraction in naïve ventricular myocytes, but not in cells pretreated with 1 microM U50,488H for 24 h. In ventricular myocytes incubated for 24 h with 1 microM U50,488H together with 1 microM chelerythrine or 1 microM GF109203X, PKC inhibitors, or 0.1 microM epsilonV1-2 peptide, a selective inhibitor of PKC-epsilon, 30 microM U50,488H still produced the inhibitory effect on the electrically-induced [Ca(2+)](i) transient as it did in naïve ventricular myocytes. Chronic treatment of ventricular myocytes with U50,488H and chelerythrine also attenuated the development of tolerance to acute U50,488H on cyclic AMP accumulation. Cells exposed to chelerythrine, GF109203X, or epsilonV1-2 peptide alone did not show an altered [Ca(2+)](i) response to U50,488H. These results indicate that activation of PKC-epsilon is a critical step in the development of tolerance in the kappa-OR.
Persistent Identifierhttp://hdl.handle.net/10722/49303
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhou, JJen_HK
dc.contributor.authorBian, JSen_HK
dc.contributor.authorPei, JMen_HK
dc.contributor.authorWu, Sen_HK
dc.contributor.authorLi, HYen_HK
dc.contributor.authorWong, TMen_HK
dc.date.accessioned2008-06-12T06:38:55Z-
dc.date.available2008-06-12T06:38:55Z-
dc.date.issued2002en_HK
dc.identifier.citationBritish Journal of Pharmacology, 2002, v. 135 n. 7, p. 1675-1784en_HK
dc.identifier.issn0007-1188en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49303-
dc.description.abstractThe role of protein kinase C-epsilon (PKC-epsilon) in the development of kappa-opioid receptor (kappa-OR) tolerance to the effects of trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl) (U50,488H), the selective agonist of kappa-OR, was determined in rat ventricular myocytes. Incubation of ventricular myocytes with 1 microM U50,488H for 24 h significantly attenuated the inhibitory effects of 30 microM U50,488H on the electrically-induced [Ca(2+)](i) transient and forskolin-stimulated cyclic AMP accumulation, indicating the development of tolerance to the kappa-OR agonist. Chronic treatment of ventricular myocytes with U50,488H also induced translocation of PKC-epsilon to the particulate fraction. On the other hand, administration of 30 microM U50,488H for 10 min induced translocation of PKC-alpha to the particulate fraction in naïve ventricular myocytes, but not in cells pretreated with 1 microM U50,488H for 24 h. In ventricular myocytes incubated for 24 h with 1 microM U50,488H together with 1 microM chelerythrine or 1 microM GF109203X, PKC inhibitors, or 0.1 microM epsilonV1-2 peptide, a selective inhibitor of PKC-epsilon, 30 microM U50,488H still produced the inhibitory effect on the electrically-induced [Ca(2+)](i) transient as it did in naïve ventricular myocytes. Chronic treatment of ventricular myocytes with U50,488H and chelerythrine also attenuated the development of tolerance to acute U50,488H on cyclic AMP accumulation. Cells exposed to chelerythrine, GF109203X, or epsilonV1-2 peptide alone did not show an altered [Ca(2+)](i) response to U50,488H. These results indicate that activation of PKC-epsilon is a critical step in the development of tolerance in the kappa-OR.en_HK
dc.format.extent388 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.subjectToleranceen_HK
dc.subjectProtein kinase C-epsilonen_HK
dc.subjectκ-opioid receptoren_HK
dc.subjectVentricular myocytesen_HK
dc.titleRole of protein kinase C-epsilon in the development of κ-opioid receptor tolerance to U50,488H in rat ventricular myocytesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0007-1188&volume=135&issue=7&spage=1675&epage=1784&date=2002&atitle=Role+of+protein+kinase+C-epsilon+in+the+development+of+κ-opioid+receptor+tolerance+to+U50,488H+in+rat+ventricular+myocytesen_HK
dc.identifier.emailWong, TM: wongtakm@hkucc.hku.hken_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1038/sj.bjp.0704640en_HK
dc.identifier.pmid11934807-
dc.identifier.pmcidPMC1573305en_HK
dc.identifier.scopuseid_2-s2.0-0036965561-
dc.identifier.isiWOS:000174940800011-

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