A new cyclic AMP-independent, G(s)-mediated stimulatory mechanism via the adenosine A(2a) receptor in the intact cardiac cell

The objectives of this study were to investigate the mechanism underlying the adenosine A(2a) receptor (A(2a)R)-mediated positive inotropic response and to define its contractile function using chick embryo ventricular cells as a model, Activation of the A(2a)R 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(2a)R agonist 2-[4-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine and the beta-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(2a)R-mediated stimulation of contractility or the L-type calcium channel, while it completely abolished the iso-proterenol effects, Activation of the A(2a)R had no effect on Na+/Ca2+ exchange or inositol 1,4,5-trisphosphate accumulation, Blocking of the A(2a)R resulted in unopposed A(1) receptor-mediated inhibitory effects and led to an inhibition of basal contractility and an enhanced anti-adrenergic effect by A(1) agonist, The adenosine A(2a) receptor mediates a new cyclic AMP-independent mechanism and a new contractile function in the cardiac cell.