Isoproterenol antagonistic effect of 2',5'-dideoxyadenosine in the isolated perfused guinea-pig heart

In this study the effects of 2',5'-dideoxyadenosine (DDA), an agonist of the intracellular adenosine binding site (P-site), on myocardial contractility, coronary resistance and cAMP-metabolism in the isolated guinea-pig heart were compared with those of adenosine. DDA (20-150 microM), like adenosine, dose dependently and reversibly inhibited the positive inotropic and chronotropic effect of beta-adrenergic stimulation with isoproterenol (8-54 pmol) up to 70% and 50%, respectively. In contrast to the known vasodilatory action of adenosine, however, basal coronary resistance remained unchanged with DDA. The antiadrenergic action of DDA was parallelled by changes in cAMP release from heart: stimulation with isoproterenol (16 pmol) increased cAMP release from 1.5 +/- 0.14 pmol cAMP/min under basal conditions to 5.2 +/- 0.45 pmol/min (mean +/- SE; n = 4). This increase was inhibited by 49% in presence of DDA (90 microM). Theophylline (50 microM), a well known antagonist of extracellular adenosine receptors, did not alter the potency of DDA. Our findings demonstrate, that DDA does not alter basal coronary flow but exerts a potent antiadrenergic action in heart which is P-site mediated.