Adenosine A2a-receptor activation enhances cardiomyocyte shortening via Ca2+-independent and -dependent mechanisms
dc.contributor.author | Woodiwiss, Angela J. | |
dc.contributor.author | Honeyman, Thomas W. | |
dc.contributor.author | Fenton, Richard A. | |
dc.contributor.author | Dobson, James G. Jr. | |
dc.date | 2022-08-11T08:10:16.000 | |
dc.date.accessioned | 2022-08-23T17:02:02Z | |
dc.date.available | 2022-08-23T17:02:02Z | |
dc.date.issued | 1999-05-18 | |
dc.date.submitted | 2008-06-09 | |
dc.identifier.citation | Am J Physiol. 1999 May;276(5 Pt 2):H1434-41. | |
dc.identifier.issn | 0002-9513 (Print) | |
dc.identifier.pmid | 10330225 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/44135 | |
dc.description.abstract | 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. | |
dc.language.iso | en_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.url | http://ajpheart.physiology.org/content/276/5/H1434.full.pdf+html | |
dc.subject | Adenosine | |
dc.subject | Adrenergic beta-Agonists | |
dc.subject | Animals | |
dc.subject | Antihypertensive Agents | |
dc.subject | Calcium | |
dc.subject | Carotenoids | |
dc.subject | Isoproterenol | |
dc.subject | Male | |
dc.subject | Muscle Fibers | |
dc.subject | Myocardial Contraction | |
dc.subject | Myocardium | |
dc.subject | Oxygenases | |
dc.subject | Pertussis Toxin | |
dc.subject | Phenethylamines | |
dc.subject | Rats | |
dc.subject | Rats, Sprague-Dawley | |
dc.subject | Receptors, Adrenergic, alpha-2 | |
dc.subject | Virulence Factors, Bordetella | |
dc.subject | Xanthines | |
dc.subject | Physiology | |
dc.title | Adenosine A2a-receptor activation enhances cardiomyocyte shortening via Ca2+-independent and -dependent mechanisms | |
dc.type | Journal Article | |
dc.source.journaltitle | The American journal of physiology | |
dc.source.volume | 276 | |
dc.source.issue | 5 Pt 2 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/physio_pp/18 | |
dc.identifier.contextkey | 521870 | |
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.submissionpath | physio_pp/18 | |
dc.contributor.department | Department of Physiology | |
dc.source.pages | H1434-41 |