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dc.contributor.authorDobson, James G. Jr.
dc.date2022-08-11T08:10:16.000
dc.date.accessioned2022-08-23T17:02:12Z
dc.date.available2022-08-23T17:02:12Z
dc.date.issued1983-02-01
dc.date.submitted2008-06-09
dc.identifier.citationCirc Res. 1983 Feb;52(2):151-60.
dc.identifier.issn0009-7330 (Print)
dc.identifier.pmid6297829
dc.identifier.urihttp://hdl.handle.net/20.500.14038/44168
dc.description.abstractThe properties of adenosine inhibition of catecholamine-induced responses were investigated, using an isolated rat heart preparation. Perfusion of hearts with 0.1 microM isoproterenol increased myocardial cAMP content 2.8-fold, activation of cAMP-dependent protein kinase 4.4-fold, phosphorylase a formation 3.4-fold, left ventricular pressure 1.8-fold, rate of ventricular pressure development 2.1-fold, and rate of ventricular relaxation 2.2-fold within 1 minute. When perfused with the isoproterenol, 10 microM adenosine reduced the catecholamine-produced increase in cAMP, cAMP-dependent protein kinase, and phosphorylase by 30-40%, and the elevation in left ventricular pressure and rate of ventricular pressure development by 40-70% within 40 seconds. More than 2 minutes were required for the nucleoside to significantly reduce the isoproterenol-elicited increase in the rate of ventricular relaxation. Perfusion of adenosine alone at concentrations from 0.1 to 10 microM were without effect on the above parameters. Theophylline at 50 microM had no effect alone on the above parameters but blocked the inhibitory actions of adenosine on the isoproterenol-induced responses. In the presence of 15 mM Mg++ adenosine reduced by approximately 56% the 2-fold increase in myocardial membrane adenylate cyclase activity produced by 1 microM isoproterenol without affecting basal or fluoride-stimulated activity. Adenosine also reduced the isoproterenol-induced increase in enzyme activity assayed at 1-2 mM Mg++, a level that more closely approximates the intracellular activity of the ion. The results suggest that physiological concentrations of adenosine attenuate the catecholamine-induced increase in cAMP content, cAMP-dependent protein kinase activation, phosphorylase a formation, and contractile parameters in the working heart, via reducing the beta-adrenergic activation of adenylate cyclase.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6297829&dopt=Abstract ">Link to article in PubMed</a>
dc.relation.urlhttp://circres.ahajournals.org/content/52/2/151.long
dc.subject2-Chloroadenosine
dc.subjectAdenosine
dc.subjectAdenylate Cyclase
dc.subjectAnimals
dc.subjectCyclic AMP
dc.subjectGlycogen
dc.subjectHeart Ventricles
dc.subjectIsoproterenol
dc.subjectMale
dc.subjectMyocardial Contraction
dc.subjectMyocardium
dc.subjectPhosphorylases
dc.subjectProtein Kinases
dc.subjectRats
dc.subjectRats, Inbred Strains
dc.subjectTime Factors
dc.subjectCardiovascular Diseases
dc.subjectCellular and Molecular Physiology
dc.subjectPhysiology
dc.titleMechanism of adenosine inhibition of catecholamine-induced responses in heart
dc.typeJournal Article
dc.source.journaltitleCirculation research
dc.source.volume52
dc.source.issue2
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/physio_pp/5
dc.identifier.contextkey521857
html.description.abstract<p>The properties of adenosine inhibition of catecholamine-induced responses were investigated, using an isolated rat heart preparation. Perfusion of hearts with 0.1 microM isoproterenol increased myocardial cAMP content 2.8-fold, activation of cAMP-dependent protein kinase 4.4-fold, phosphorylase a formation 3.4-fold, left ventricular pressure 1.8-fold, rate of ventricular pressure development 2.1-fold, and rate of ventricular relaxation 2.2-fold within 1 minute. When perfused with the isoproterenol, 10 microM adenosine reduced the catecholamine-produced increase in cAMP, cAMP-dependent protein kinase, and phosphorylase by 30-40%, and the elevation in left ventricular pressure and rate of ventricular pressure development by 40-70% within 40 seconds. More than 2 minutes were required for the nucleoside to significantly reduce the isoproterenol-elicited increase in the rate of ventricular relaxation. Perfusion of adenosine alone at concentrations from 0.1 to 10 microM were without effect on the above parameters. Theophylline at 50 microM had no effect alone on the above parameters but blocked the inhibitory actions of adenosine on the isoproterenol-induced responses. In the presence of 15 mM Mg++ adenosine reduced by approximately 56% the 2-fold increase in myocardial membrane adenylate cyclase activity produced by 1 microM isoproterenol without affecting basal or fluoride-stimulated activity. Adenosine also reduced the isoproterenol-induced increase in enzyme activity assayed at 1-2 mM Mg++, a level that more closely approximates the intracellular activity of the ion. The results suggest that physiological concentrations of adenosine attenuate the catecholamine-induced increase in cAMP content, cAMP-dependent protein kinase activation, phosphorylase a formation, and contractile parameters in the working heart, via reducing the beta-adrenergic activation of adenylate cyclase.</p>
dc.identifier.submissionpathphysio_pp/5
dc.contributor.departmentDepartment of Physiology
dc.source.pages151-60


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