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dc.contributor.authorSawmiller, Darrell R.
dc.contributor.authorFenton, Richard A.
dc.contributor.authorDobson, James G. Jr.
dc.date2022-08-11T08:09:31.000
dc.date.accessioned2022-08-23T16:33:54Z
dc.date.available2022-08-23T16:33:54Z
dc.date.issued1998-03-05
dc.date.submitted2007-12-21
dc.identifier.citation<p>Am J Physiol. 1998 Feb;274(2 Pt 2):H627-35.</p>
dc.identifier.issn0002-9513 (Print)
dc.identifier.doi10.1152/ajpheart.1998.274.2.H627
dc.identifier.pmid9486267
dc.identifier.urihttp://hdl.handle.net/20.500.14038/38211
dc.description.abstractIn the heart, endogenous adenosine attenuates the beta-adrenergic-elicited increase in contractile performance via activation of adenosine A1 receptors. It has been recently reported that this function of adenosine becomes more pronounced with myocardial maturation. The purpose of the present study was to determine whether mature hearts possess a greater sensitivity than immature hearts to this antiadrenergic effect of adenosine. Isolated perfused hearts or atria from immature (ca. 23 days) and mature (ca. 80 days) rats were stimulated with isoproterenol (Iso), a beta-adrenergic agonist, at 10(-8) M and concomitantly exposed to increasing concentrations of 2-chloro-N6-cyclopentyladenosine (CCPA), a highly selective and potent adenosine A1-receptor agonist, from 10(-12) to 10(-6) M. CCPA at 10(-10)-10(-6) M dose dependently reduced the Iso-elicited contractile response more in immature than in mature hearts or atria. At 10(-6) M, CCPA reduced the Iso-elicited contractile response by 103% in immature hearts and by 55% in mature hearts. These effects of CCPA were attenuated by the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine at 10(-7) M. In additional experiments, CCPA exhibited similar effectiveness in reducing the spontaneous heart rate of immature and mature hearts, an effect also mediated by activation of adenosine A1 receptors. Similar to CCPA, the adenosine A1-receptor agonist R-N6-(2-phenylisopropyl)adenosine reduced the Iso-elicited contractile response more in immature than in mature hearts, albeit with less effectiveness than CCPA. In agreement with these results, CCPA reduced Iso-elicited adenylyl cyclase activity more in immature than in mature hearts. Overall, in contrast with our original hypothesis, these results indicate that immature hearts display greater sensitivity than mature hearts to the antiadrenergic effect of adenosine A1-receptor activation.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9486267&dopt=Abstract ">Link to article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1152/ajpheart.1998.274.2.H627
dc.subjectAdenosine
dc.subjectAdenylate Cyclase
dc.subjectAdrenergic beta-Agonists
dc.subjectAging
dc.subjectAnimals
dc.subjectHeart
dc.subjectHeart Rate
dc.subjectIsoproterenol
dc.subjectMale
dc.subjectMyocardial Contraction
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectReceptors, Purinergic P1
dc.subjectVasodilator Agents
dc.subjectXanthines
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleMyocardial adenosine A1-receptor sensitivity during juvenile and adult stages of maturation
dc.typeArticle
dc.source.journaltitleThe American journal of physiology
dc.source.volume274
dc.source.issue2 Pt 2
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/109
dc.identifier.contextkey407404
html.description.abstract<p>In the heart, endogenous adenosine attenuates the beta-adrenergic-elicited increase in contractile performance via activation of adenosine A1 receptors. It has been recently reported that this function of adenosine becomes more pronounced with myocardial maturation. The purpose of the present study was to determine whether mature hearts possess a greater sensitivity than immature hearts to this antiadrenergic effect of adenosine. Isolated perfused hearts or atria from immature (ca. 23 days) and mature (ca. 80 days) rats were stimulated with isoproterenol (Iso), a beta-adrenergic agonist, at 10(-8) M and concomitantly exposed to increasing concentrations of 2-chloro-N6-cyclopentyladenosine (CCPA), a highly selective and potent adenosine A1-receptor agonist, from 10(-12) to 10(-6) M. CCPA at 10(-10)-10(-6) M dose dependently reduced the Iso-elicited contractile response more in immature than in mature hearts or atria. At 10(-6) M, CCPA reduced the Iso-elicited contractile response by 103% in immature hearts and by 55% in mature hearts. These effects of CCPA were attenuated by the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine at 10(-7) M. In additional experiments, CCPA exhibited similar effectiveness in reducing the spontaneous heart rate of immature and mature hearts, an effect also mediated by activation of adenosine A1 receptors. Similar to CCPA, the adenosine A1-receptor agonist R-N6-(2-phenylisopropyl)adenosine reduced the Iso-elicited contractile response more in immature than in mature hearts, albeit with less effectiveness than CCPA. In agreement with these results, CCPA reduced Iso-elicited adenylyl cyclase activity more in immature than in mature hearts. Overall, in contrast with our original hypothesis, these results indicate that immature hearts display greater sensitivity than mature hearts to the antiadrenergic effect of adenosine A1-receptor activation.</p>
dc.identifier.submissionpathoapubs/109
dc.contributor.departmentDepartment of Physiology
dc.source.pagesH627-35


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