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Article: Increased PKA activity and its influence on isoprenaline-stimulated L-type Ca2+ channels in the heart from ovariectomized rats

TitleIncreased PKA activity and its influence on isoprenaline-stimulated L-type Ca2+ channels in the heart from ovariectomized rats
Authors
KeywordsOestrogen
β-adrenoceptor
Protein kinase A
Ovariectomy
L-type Ca2+ channel
Issue Date2005
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjp
Citation
British Journal of Pharmacology, 2005, v. 144 n. 7, p. 972-981 How to Cite?
AbstractWe previously showed that oestrogen confers cardioprotection by downregulating the cardiac beta1-adrenoceptor (beta1-AR). The present study examined the effect of oestrogen on the post beta1-AR signalling cascade, with particular emphasis on the activity of protein kinase A (PKA) and its influence on the L-type Ca2+ channel. Three groups of adult female Sprague-Dawley rats were used: sham-operated controls, bilaterally ovariectomized (Ovx) rats, and Ovx rats with oestrogen replacement (Ovx + E2), which restored the oestrogen concentration to normal. The electrically induced intracellular Ca2+ transient (E[Ca2+]i), 45Ca(2+)-uptake through cardiac L-type Ca2+ channels (Ca2+ channels), heart rate and force of contraction in response to beta-AR stimulation with 10 nM isoprenaline (Iso) in hearts from Ovx rats were significantly greater than those of control and Ovx + E2 rats. The basal and Iso-induced PKA activities were also higher in hearts from Ovx rats. KT5720, a selective PKA inhibitor, completely inhibited its potentiating effect on basal Ca2+ channel activity in the Ovx rat heart. On the other hand, expression of G proteins (G(alpha)s and G(alpha)i1-3)), basal and forskolin-stimulated cAMP accumulation, and responsiveness of PKA to cAMP, were not altered by Ovx. Interestingly, the PKA inhibitor at the same concentration significantly reduced the increases in PKA activity and Ca2+ channel activity upon beta-AR stimulation in all three groups of rats and the inhibitions were significantly greater in the Ovx rat than in the other two groups of rats. This study provides the first evidence that, in addition to downregulation of beta1-AR shown previously, suppression of PKA activity, which is partly responsible for the suppressed Ca2+ channel activity, also determines the E[Ca2+]i and cardiac contractility following beta-AR stimulation in the female rat.
Persistent Identifierhttp://hdl.handle.net/10722/49284
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKam, KWLen_HK
dc.contributor.authorKravtsov, GMen_HK
dc.contributor.authorLiu, Jen_HK
dc.contributor.authorWong, TMen_HK
dc.date.accessioned2008-06-12T06:38:30Z-
dc.date.available2008-06-12T06:38:30Z-
dc.date.issued2005en_HK
dc.identifier.citationBritish Journal of Pharmacology, 2005, v. 144 n. 7, p. 972-981en_HK
dc.identifier.issn0007-1188en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49284-
dc.description.abstractWe previously showed that oestrogen confers cardioprotection by downregulating the cardiac beta1-adrenoceptor (beta1-AR). The present study examined the effect of oestrogen on the post beta1-AR signalling cascade, with particular emphasis on the activity of protein kinase A (PKA) and its influence on the L-type Ca2+ channel. Three groups of adult female Sprague-Dawley rats were used: sham-operated controls, bilaterally ovariectomized (Ovx) rats, and Ovx rats with oestrogen replacement (Ovx + E2), which restored the oestrogen concentration to normal. The electrically induced intracellular Ca2+ transient (E[Ca2+]i), 45Ca(2+)-uptake through cardiac L-type Ca2+ channels (Ca2+ channels), heart rate and force of contraction in response to beta-AR stimulation with 10 nM isoprenaline (Iso) in hearts from Ovx rats were significantly greater than those of control and Ovx + E2 rats. The basal and Iso-induced PKA activities were also higher in hearts from Ovx rats. KT5720, a selective PKA inhibitor, completely inhibited its potentiating effect on basal Ca2+ channel activity in the Ovx rat heart. On the other hand, expression of G proteins (G(alpha)s and G(alpha)i1-3)), basal and forskolin-stimulated cAMP accumulation, and responsiveness of PKA to cAMP, were not altered by Ovx. Interestingly, the PKA inhibitor at the same concentration significantly reduced the increases in PKA activity and Ca2+ channel activity upon beta-AR stimulation in all three groups of rats and the inhibitions were significantly greater in the Ovx rat than in the other two groups of rats. This study provides the first evidence that, in addition to downregulation of beta1-AR shown previously, suppression of PKA activity, which is partly responsible for the suppressed Ca2+ channel activity, also determines the E[Ca2+]i and cardiac contractility following beta-AR stimulation in the female rat.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.subjectOestrogenen_HK
dc.subjectβ-adrenoceptoren_HK
dc.subjectProtein kinase Aen_HK
dc.subjectOvariectomyen_HK
dc.subjectL-type Ca2+ channelen_HK
dc.titleIncreased PKA activity and its influence on isoprenaline-stimulated L-type Ca2+ channels in the heart from ovariectomized ratsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0007-1188&volume=144&issue=7&spage=972&epage=981&date=2005&atitle=Increased+PKA+activity+and+its+influence+on+isoprenaline-stimulated+L-type+Ca2++channels+in+the+heart+from+ovariectomized+ratsen_HK
dc.identifier.emailKam, KWL: kam_wan_lung@hotmail.comen_HK
dc.identifier.emailKravtsov, GM: gmkravts@HKUCC.hku.hken_HK
dc.identifier.emailLiu, J: liuj@hkusua.hku.hken_HK
dc.identifier.emailWong, TM: wongtakm@hkucc.hku.hken_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1038/sj.bjp.0706123en_HK
dc.identifier.pmid15685204-
dc.identifier.pmcidPMC1576077en_HK
dc.identifier.scopuseid_2-s2.0-17844404538-
dc.identifier.hkuros106453-
dc.identifier.isiWOS:000228649700012-

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