HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liang, B. T. Articles by Morley, J. F. Search for Related Content PubMed PubMed Citation Articles by Liang, B. T. Articles by Morley, J. F. Social Bookmarking                      What's this?

Volume 271, Number 31, Issue of August 2, 1996 pp. 18678-18685
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

---

A New Cyclic AMP-independent, G_s-mediated Stimulatory Mechanism via the Adenosine A_2a Receptor in the Intact Cardiac Cell

(Received for publication, July 5, 1995, and in revised form, April 25, 1996)

From the Departments of Medicine and Pharmacology and the Cardiovascular Division, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104

The objectives of this study were to investigate the mechanism underlying the adenosine A_2a receptor (A_2aR)-mediated positive inotropic response and to define its contractile function using chick embryo ventricular cells as a model. Activation of the A_2aR caused a marked stimulation of calcium entry and cell contractility, which were blocked by verapamil or nifedipine. The effects elicited by maximal concentrations of the A_2aR agonist 2-[4-(2-carboxyethyl)phenylethylamino]-5-N-ethylcarboxamidoadenosine and the -adrenergic agonist isoproterenol were additive, indicating that the two receptors do not share a common stimulatory mechanism. The cAMP antagonist (R_p)-adenosine cyclic 3:5-monophosphorothioate was ineffective in inhibiting the A_2aR-mediated stimulation of contractility or the L-type calcium channel, while it completely abolished the isoproterenol effects. Activation of the A_2aR had no effect on Na⁺/Ca²⁺ exchange or inositol 1,4,5-trisphosphate accumulation. Blocking of the A_2aR resulted in unopposed A₁ receptor-mediated inhibitory effects and led to an inhibition of basal contractility and an enhanced anti-adrenergic effect by A₁ agonist. The adenosine A_2a receptor mediates a new cyclic AMP-independent mechanism and a new contractile function in the cardiac cell.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. G. Dobson Jr., L. G. Shea, and R. A. Fenton Adenosine A2A and {beta}-adrenergic calcium transient and contractile responses in rat ventricular myocytes Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2364 - H2372. [Abstract] [Full Text] [PDF]

				E. I. Tikh, R. A. Fenton, and J. G. Dobson Jr. Contractile effects of adenosine A1 and A2A receptors in isolated murine hearts Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H348 - H356. [Abstract] [Full Text] [PDF]

				W. Wang, W. Zhu, S. Wang, D. Yang, M. T. Crow, R.-P. Xiao, and H. Cheng Sustained {beta}1-Adrenergic Stimulation Modulates Cardiac Contractility by Ca2+/Calmodulin Kinase Signaling Pathway Circ. Res., October 15, 2004; 95(8): 798 - 806. [Abstract] [Full Text] [PDF]

				M. E. Olah and C. C. Caldwell Adenosine Receptors and Mammalian Toll-Like Receptors: Synergism in Macrophages Mol. Interv., October 1, 2003; 3(7): 370 - 374. [Abstract] [Full Text]

				T. E. Meyer, E. S. Chung, S. Perlini, G. R. Norton, A. J. Woodiwiss, M. Lorbar, R. A. Fenton, and J. G. Dobson Jr Antiadrenergic Effects of Adenosine in Pressure Overload Hypertrophy Hypertension, March 1, 2001; 37(3): 862 - 868. [Abstract] [Full Text] [PDF]

				T. S. Monahan, D. R. Sawmiller, R. A. Fenton, and J. G. Dobson Jr. Adenosine A2a-receptor activation increases contractility in isolated perfused hearts Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1472 - H1481. [Abstract] [Full Text] [PDF]

				A. J. Woodiwiss, T. W. Honeyman, R. A. Fenton, and J. G. Dobson Jr. Adenosine A2a-receptor activation enhances cardiomyocyte shortening via Ca2+-independent and -dependent mechanisms Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1434 - H1441. [Abstract] [Full Text] [PDF]

				G. R. Norton, A. J. Woodiwiss, R. J. McGinn, M. Lorbar, E. S. Chung, T. W. Honeyman, R. A. Fenton, J. G. Dobson Jr., and T. E. Meyer Adenosine A1 receptor-mediated antiadrenergic effects are modulated by A2a receptor activation in rat heart Am J Physiol Heart Circ Physiol, February 1, 1999; 276(2): H341 - H349. [Abstract] [Full Text] [PDF]

				D. R. Sawmiller, R. A. Fenton, and J. G. Dobson Jr. Myocardial adenosine A1-receptor sensitivity during juvenile and adult stages of maturation Am J Physiol Heart Circ Physiol, February 1, 1998; 274(2): H627 - H635. [Abstract] [Full Text] [PDF]

				D. R. Wagner, A. Combes, C. McTiernan, V. J. Sanders, B. Lemster, and A. M. Feldman Adenosine Inhibits Lipopolysaccharide-Induced Cardiac Expression of Tumor Necrosis Factor-{alpha} Circ. Res., January 23, 1998; 82(1): 47 - 56. [Abstract] [Full Text] [PDF]

				I. Feoktistov and I. Biaggioni Adenosine A2B Receptors Pharmacol. Rev., December 1, 1997; 49(4): 381 - 402. [Abstract] [Full Text] [PDF]

				E. Podrasky, D. Xu, and B. T. Liang A novel phospholipase C- and cAMP-independent positive inotropic mechanism via a P2 purinoceptor Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2380 - H2387. [Abstract] [Full Text] [PDF]

				E. L. Kilpatrick, P. Narayan, R. M. Mentzer Jr., and R. D. Lasley Cardiac myocyte adenosine A2a receptor activation fails to alter cAMP or contractility: role of receptor localization Am J Physiol Heart Circ Physiol, March 1, 2002; 282(3): H1035 - H1040. [Abstract] [Full Text] [PDF]