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Article: Testosterone-augmented contractile responses to α1- and β1-adrenoceptor stimulation are associated with increased activities of RyR, SERCA, and NCX in the heart

TitleTestosterone-augmented contractile responses to α1- and β1-adrenoceptor stimulation are associated with increased activities of RyR, SERCA, and NCX in the heart
Authors
Issue Date2009
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpcell.physiology.org/
Citation
American Journal Of Physiology - Cell Physiology, 2009, v. 296 n. 4, p. C766-C782 How to Cite?
AbstractWe hypothesized that testosterone at physiological levels enhances cardiac contractile responses to stimulation of both α1- and β1-adrenoceptors by increasing Ca2+ release from the sarcoplasmic reticulum (SR) and speedier removal of Ca2+ from cytosol via Ca2+-regulatory proteins. We first determined the left ventricular developed pressure, velocity of contraction and relaxation, and heart rate in perfused hearts isolated from control rats, orchiectomized rats, and orchiectomized rats without and with testosterone replacement (200 μg/100 g body wt) in the presence of norepinephrine (10-7 M), the α1-adrenoceptor agonist phenylephrine (10-6 M), or the nonselective β-adrenoceptor agonist isoprenaline (10-7 M) in the presence of 5 × 10-7 M ICI-118,551, a β2- adrenoceptor antagonist. Next, we determined the amplitudes of intracellular Ca2+ concentration transients induced by electrical stimulation or caffeine, which represent, respectively, Ca2+ release via the ryanodine receptor (RyR) or releasable Ca2+ in the SR, in ventricular myocytes isolated from the three groups of rats. We also measured 45Ca2+ release via the RyR. We then determined the time to 50% decay of both transients, which represents, respectively, Ca2+ reuptake by sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and removal via the sarcolemmal Na+/Ca2+ exchanger (NCX). We correlated Ca2+ removal from the cytosol with activities of SERCA and its regulator phospholamban as well as NCX. The results showed that testosterone at physiological levels enhanced positive inotropic and lusitropic responses to stimulation of α1- and β1- adrenoceptors via the androgen receptor. The increased contractility and speedier relaxation were associated with increased Ca2+ release via the RyR and faster Ca2+ removal out of the cytosol via SERCA and NCX. Copyright © 2009 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/188346
ISSN
2015 Impact Factor: 3.395
2015 SCImago Journal Rankings: 1.893
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTsang, Sen_US
dc.contributor.authorWong, SSCen_US
dc.contributor.authorWu, Sen_US
dc.contributor.authorKravtsov, GMen_US
dc.contributor.authorWong, TMen_US
dc.date.accessioned2013-09-03T04:02:51Z-
dc.date.available2013-09-03T04:02:51Z-
dc.date.issued2009en_US
dc.identifier.citationAmerican Journal Of Physiology - Cell Physiology, 2009, v. 296 n. 4, p. C766-C782en_US
dc.identifier.issn0363-6143en_US
dc.identifier.urihttp://hdl.handle.net/10722/188346-
dc.description.abstractWe hypothesized that testosterone at physiological levels enhances cardiac contractile responses to stimulation of both α1- and β1-adrenoceptors by increasing Ca2+ release from the sarcoplasmic reticulum (SR) and speedier removal of Ca2+ from cytosol via Ca2+-regulatory proteins. We first determined the left ventricular developed pressure, velocity of contraction and relaxation, and heart rate in perfused hearts isolated from control rats, orchiectomized rats, and orchiectomized rats without and with testosterone replacement (200 μg/100 g body wt) in the presence of norepinephrine (10-7 M), the α1-adrenoceptor agonist phenylephrine (10-6 M), or the nonselective β-adrenoceptor agonist isoprenaline (10-7 M) in the presence of 5 × 10-7 M ICI-118,551, a β2- adrenoceptor antagonist. Next, we determined the amplitudes of intracellular Ca2+ concentration transients induced by electrical stimulation or caffeine, which represent, respectively, Ca2+ release via the ryanodine receptor (RyR) or releasable Ca2+ in the SR, in ventricular myocytes isolated from the three groups of rats. We also measured 45Ca2+ release via the RyR. We then determined the time to 50% decay of both transients, which represents, respectively, Ca2+ reuptake by sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and removal via the sarcolemmal Na+/Ca2+ exchanger (NCX). We correlated Ca2+ removal from the cytosol with activities of SERCA and its regulator phospholamban as well as NCX. The results showed that testosterone at physiological levels enhanced positive inotropic and lusitropic responses to stimulation of α1- and β1- adrenoceptors via the androgen receptor. The increased contractility and speedier relaxation were associated with increased Ca2+ release via the RyR and faster Ca2+ removal out of the cytosol via SERCA and NCX. Copyright © 2009 the American Physiological Society.en_US
dc.languageengen_US
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpcell.physiology.org/en_US
dc.relation.ispartofAmerican Journal of Physiology - Cell Physiologyen_US
dc.subject.meshAdrenergic Agonists - Pharmacologyen_US
dc.subject.meshAdrenergic Alpha-1 Receptor Agonistsen_US
dc.subject.meshAdrenergic Beta-1 Receptor Agonistsen_US
dc.subject.meshAdrenergic Beta-Antagonists - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCaffeine - Pharmacologyen_US
dc.subject.meshCalcium Radioisotopesen_US
dc.subject.meshCalcium Signaling - Drug Effectsen_US
dc.subject.meshCalcium-Binding Proteins - Metabolismen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshElectric Stimulationen_US
dc.subject.meshIsoproterenol - Pharmacologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMyocardial Contraction - Drug Effectsen_US
dc.subject.meshMyocardium - Enzymology - Metabolismen_US
dc.subject.meshNorepinephrine - Pharmacologyen_US
dc.subject.meshOrchiectomyen_US
dc.subject.meshPhenylephrine - Pharmacologyen_US
dc.subject.meshPropanolamines - Pharmacologyen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshReceptors, Adrenergic, Alpha-1 - Metabolismen_US
dc.subject.meshReceptors, Adrenergic, Beta-1 - Metabolismen_US
dc.subject.meshReceptors, Androgen - Metabolismen_US
dc.subject.meshRyanodine Receptor Calcium Release Channel - Metabolismen_US
dc.subject.meshSarcoplasmic Reticulum Calcium-Transporting Atpases - Metabolismen_US
dc.subject.meshSodium-Calcium Exchanger - Metabolismen_US
dc.subject.meshTestosterone - Administration & Dosage - Metabolismen_US
dc.subject.meshTime Factorsen_US
dc.subject.meshVentricular Function, Left - Drug Effectsen_US
dc.subject.meshVentricular Pressure - Drug Effectsen_US
dc.titleTestosterone-augmented contractile responses to α1- and β1-adrenoceptor stimulation are associated with increased activities of RyR, SERCA, and NCX in the hearten_US
dc.typeArticleen_US
dc.identifier.emailWong, SSC: wongstan@hku.hken_US
dc.identifier.authorityWong, SSC=rp01789en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1152/ajpcell.00193.2008en_US
dc.identifier.pmid19336623-
dc.identifier.scopuseid_2-s2.0-65649113668en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-65649113668&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume296en_US
dc.identifier.issue4en_US
dc.identifier.spageC766en_US
dc.identifier.epageC782en_US
dc.identifier.isiWOS:000264753200013-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridTsang, S=8597451500en_US
dc.identifier.scopusauthoridWong, SSC=55451201000en_US
dc.identifier.scopusauthoridWu, S=7408443898en_US
dc.identifier.scopusauthoridKravtsov, GM=7003811092en_US
dc.identifier.scopusauthoridWong, TM=7403531434en_US

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