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dc.contributor.authorWoodiwiss, Angela J.
dc.contributor.authorHoneyman, Thomas W.
dc.contributor.authorFenton, Richard A.
dc.contributor.authorDobson, James G. Jr.
dc.date2022-08-11T08:10:16.000
dc.date.accessioned2022-08-23T17:02:02Z
dc.date.available2022-08-23T17:02:02Z
dc.date.issued1999-05-18
dc.date.submitted2008-06-09
dc.identifier.citationAm J Physiol. 1999 May;276(5 Pt 2):H1434-41.
dc.identifier.issn0002-9513 (Print)
dc.identifier.pmid10330225
dc.identifier.urihttp://hdl.handle.net/20.500.14038/44135
dc.description.abstractAdenosine A2a receptor (A2aR) stimulation enhances the shortening of ventricular myocytes. Whether the A2aR-mediated increase in myocyte contractility is associated with alterations in the amplitude of intracellular Ca2+ transients was investigated in isolated, contracting rat ventricular myocytes using the Ca2+-sensitive fluorescent dye fura 2-AM. In the presence of intact inhibitory G protein pathways, 10(-4) M 2-p-(2-carboxyethyl)phenethyl-amino-5'-N-ethylcarboxamidoadenosine (CGS-21680), an A2aR agonist, insignificantly increased Ca2+ transients by 8 +/- 5%, whereas myocyte shortening increased by 54 +/- 1%. In contrast, 2 x 10(-7) M isoproterenol, a beta-adrenergic receptor agonist, increased Ca2+ transients by 104 +/- 15% and increased myocyte shortening by 61 +/- 6%. When A2aR were stimulated in myocytes that had the antiadrenergic actions of adenosine (Ado) abolished by either treatment with pertussis toxin (PTx) or the presence of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A1-receptor antagonist, the maximum increases in Ca2+ transients were similarly nominal (with PTx: 10(-4) M CGS-21680, 14 +/- 6% and 10(-4) M Ado, 15 +/- 4%; without PTx: 10(-5) M Ado + 2 x 10(-7) M DPCPX, 19 +/- 1%). These results indicate that compared with beta-adrenergic stimulation, which markedly increases myocyte Ca2+ transients and shortening, A2aR-mediated increases in myocyte shortening are accompanied by only modest increases in Ca2+ transients. These observations suggest that the A2aR-induced contractile effects are mediated predominantly by Ca2+-independent inotropic mechanisms.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10330225&dopt=Abstract ">Link to article in PubMed</a>
dc.relation.urlhttp://ajpheart.physiology.org/content/276/5/H1434.full.pdf+html
dc.subjectAdenosine
dc.subjectAdrenergic beta-Agonists
dc.subjectAnimals
dc.subjectAntihypertensive Agents
dc.subjectCalcium
dc.subjectCarotenoids
dc.subjectIsoproterenol
dc.subjectMale
dc.subjectMuscle Fibers
dc.subjectMyocardial Contraction
dc.subjectMyocardium
dc.subjectOxygenases
dc.subjectPertussis Toxin
dc.subjectPhenethylamines
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectReceptors, Adrenergic, alpha-2
dc.subjectVirulence Factors, Bordetella
dc.subjectXanthines
dc.subjectPhysiology
dc.titleAdenosine A2a-receptor activation enhances cardiomyocyte shortening via Ca2+-independent and -dependent mechanisms
dc.typeJournal Article
dc.source.journaltitleThe American journal of physiology
dc.source.volume276
dc.source.issue5 Pt 2
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/physio_pp/18
dc.identifier.contextkey521870
html.description.abstract<p>Adenosine A2a receptor (A2aR) stimulation enhances the shortening of ventricular myocytes. Whether the A2aR-mediated increase in myocyte contractility is associated with alterations in the amplitude of intracellular Ca2+ transients was investigated in isolated, contracting rat ventricular myocytes using the Ca2+-sensitive fluorescent dye fura 2-AM. In the presence of intact inhibitory G protein pathways, 10(-4) M 2-p-(2-carboxyethyl)phenethyl-amino-5'-N-ethylcarboxamidoadenosine (CGS-21680), an A2aR agonist, insignificantly increased Ca2+ transients by 8 +/- 5%, whereas myocyte shortening increased by 54 +/- 1%. In contrast, 2 x 10(-7) M isoproterenol, a beta-adrenergic receptor agonist, increased Ca2+ transients by 104 +/- 15% and increased myocyte shortening by 61 +/- 6%. When A2aR were stimulated in myocytes that had the antiadrenergic actions of adenosine (Ado) abolished by either treatment with pertussis toxin (PTx) or the presence of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A1-receptor antagonist, the maximum increases in Ca2+ transients were similarly nominal (with PTx: 10(-4) M CGS-21680, 14 +/- 6% and 10(-4) M Ado, 15 +/- 4%; without PTx: 10(-5) M Ado + 2 x 10(-7) M DPCPX, 19 +/- 1%). These results indicate that compared with beta-adrenergic stimulation, which markedly increases myocyte Ca2+ transients and shortening, A2aR-mediated increases in myocyte shortening are accompanied by only modest increases in Ca2+ transients. These observations suggest that the A2aR-induced contractile effects are mediated predominantly by Ca2+-independent inotropic mechanisms.</p>
dc.identifier.submissionpathphysio_pp/18
dc.contributor.departmentDepartment of Physiology
dc.source.pagesH1434-41


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