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dc.contributor.authorRomano, Fred D.
dc.contributor.authorDobson, James G. Jr.
dc.date2022-08-11T08:10:16.000
dc.date.accessioned2022-08-23T17:02:13Z
dc.date.available2022-08-23T17:02:13Z
dc.date.issued1996-01-01
dc.date.submitted2008-06-12
dc.identifier.citationLife Sci. 1996;58(6):493-502.
dc.identifier.issn0024-3205 (Print)
dc.identifier.pmid8569422
dc.identifier.urihttp://hdl.handle.net/20.500.14038/44171
dc.description.abstractInterstitial levels and release of adenosine have been shown to be greater for aged adult hearts compared to young adult hearts. Furthermore, blockade of A1 adenosine receptors in the aged adult heart prevents the reduced contractile and metabolic response to isoproterenol. The aim of this study was to determine whether there is an enhanced antiadrenergic effect of adenosine in the aged adult heart. Ventricular membranes from young and aged adult hearts were incubated in the presence of isoproterenol (ISO) and phenylisopropyladenosine (PIA) either alone or in combination. Basal and ISO-enhanced adenylyl cyclase activity were significantly reduced in the membranes from aged rats. PIA alone, at 0.1 nM to 100 microM, had no direct effect on basal adenylyl cyclase activity in membranes from either group. In the presence of either 100 nM or 1 microM ISO, 100 microM PIA significantly attenuated ISO-enhanced adenylyl cyclase activity to a greater extent in the aged adult heart membranes (78 or 48% for the aged vs. 37 or 25% for the young). Moreover, in the presence of 100 nM ISO the IC50 for the PIA concentration response curve was shifted to the left for the aged ventricular membranes as compared to the membranes from young adults (1.62 x 10(-7) M vs 1.5 x 10(-6) M, aged vs young, respectively). The enhanced inhibition of adenylyl cyclase is associated with an increase in adenosine A1 receptor density (23.7 +/- 3.5 vs 14.7 +/- 1.7 fmol/mg, aged vs young) and Kd (6.1 +/- 1.7 vs 2.2 +/- 0.5 nM, aged vs young) in the aged adult heart membranes as determined by [3H]DPCPX binding. These results suggest that the reduced response to catecholamines in the aged adult heart may be due, at least in part, to an enhanced expression of the antiadrenergic effect of adenosine on beta-adrenergic receptor mediated activation of adenylyl cyclase.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8569422&dopt=Abstract ">Link to article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1016/0024-3205(95)02314-3
dc.subjectAdenosine
dc.subjectAdenylate Cyclase
dc.subjectAdrenergic beta-Agonists
dc.subjectAging
dc.subjectAnimals
dc.subjectDrug Interactions
dc.subjectHeart
dc.subjectIsoproterenol
dc.subjectMale
dc.subjectMembranes
dc.subjectMyocardium
dc.subjectPhenylisopropyladenosine
dc.subjectRats
dc.subjectRats, Inbred F344
dc.subjectRats, Sprague-Dawley
dc.subjectReceptors, Purinergic P1
dc.subjectStimulation, Chemical
dc.subjectTritium
dc.subjectXanthines
dc.subjectCardiovascular Diseases
dc.subjectCellular and Molecular Physiology
dc.subjectPhysiology
dc.titleAdenosine attenuation of isoproterenol-stimulated adenylyl cyclase activity is enhanced with aging in the adult heart
dc.typeJournal Article
dc.source.journaltitleLife sciences
dc.source.volume58
dc.source.issue6
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/physio_pp/52
dc.identifier.contextkey523468
html.description.abstract<p>Interstitial levels and release of adenosine have been shown to be greater for aged adult hearts compared to young adult hearts. Furthermore, blockade of A1 adenosine receptors in the aged adult heart prevents the reduced contractile and metabolic response to isoproterenol. The aim of this study was to determine whether there is an enhanced antiadrenergic effect of adenosine in the aged adult heart. Ventricular membranes from young and aged adult hearts were incubated in the presence of isoproterenol (ISO) and phenylisopropyladenosine (PIA) either alone or in combination. Basal and ISO-enhanced adenylyl cyclase activity were significantly reduced in the membranes from aged rats. PIA alone, at 0.1 nM to 100 microM, had no direct effect on basal adenylyl cyclase activity in membranes from either group. In the presence of either 100 nM or 1 microM ISO, 100 microM PIA significantly attenuated ISO-enhanced adenylyl cyclase activity to a greater extent in the aged adult heart membranes (78 or 48% for the aged vs. 37 or 25% for the young). Moreover, in the presence of 100 nM ISO the IC50 for the PIA concentration response curve was shifted to the left for the aged ventricular membranes as compared to the membranes from young adults (1.62 x 10(-7) M vs 1.5 x 10(-6) M, aged vs young, respectively). The enhanced inhibition of adenylyl cyclase is associated with an increase in adenosine A1 receptor density (23.7 +/- 3.5 vs 14.7 +/- 1.7 fmol/mg, aged vs young) and Kd (6.1 +/- 1.7 vs 2.2 +/- 0.5 nM, aged vs young) in the aged adult heart membranes as determined by [3H]DPCPX binding. These results suggest that the reduced response to catecholamines in the aged adult heart may be due, at least in part, to an enhanced expression of the antiadrenergic effect of adenosine on beta-adrenergic receptor mediated activation of adenylyl cyclase.</p>
dc.identifier.submissionpathphysio_pp/52
dc.contributor.departmentDepartment of Physiology
dc.source.pages493-502


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