Inotropic effects of diadenosine monophosphate (AP(1)A) in isolated human cardiac preparations

Dependent on the number of phosphate residues, diadenosine polyphosphates ( AP(n)P) exert divergent inotropic effects in the human heart. We studied th e inotropic effects of the smallest member of this family, diadenosine mono phosphate (AP(1)A). Force of contraction was measured in an isometric setup in isolated electrically driven (0.5 Hz) preparations from human atria. AP (1)A exerted a concentration-dependent negative inotropic effect. The IC50 value was 20.2 mu M and the IC20 value was 3.1 mu M (n = 5-8). At 100 mu M AP(1)A, force of contraction declined to 50% of the predrug value after 2.5 +/- 0.5 min of incubation (n = 8). AP(1)A antagonized the positive inotrop ic effect of the beta-adrenoceptor agonist isoprenaline (10 nM). For 100 mu M AP(1)A, the time to 50% of the predrug force in the presence of isoprena line amounted to 2.3 +/- 0.2 min (n = 5). The positive inotropic and lusitr opic effects of isoprenaline were antagonized by AP(1)A. The direct (AP(1)A alone) and indirect (AP(1)A in the presence of isoprenaline) negative inot ropic effects of AP(1)A were blocked by the A(1)-adenosine receptor antagon ist 1,3-dipropyl-cyclopentyl-xanthine (DPCPX, 0.3 mu M). The inotropic effe ct of AP(1)A was not blocked by adenosine deaminase. In conclusion, AP(1)A exerts indirect and direct negative inotropic effects in the human heart th rough A, adenosine receptors. These effects might protect the heart against excessive beta-adrenergic stimulation.