Inotropic effects of diadenosine monophosphate (AP1A) 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 the inotropic effects of the smallest member of this family, diadenosine monophosphate (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 inotropic 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 isoprenaline amounted to 2.3 +/- 0.2 min (n = 5). The positive inotropic and lusitropic 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 inotropic effects of AP(1)A were blocked by the A(1)-adenosine receptor antagonist 1,3-dipropyl-cyclopentyl-xanthine (DPCPX, 0.3 mu M). The inotropic effect 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 through A, adenosine receptors. These effects might protect the heart against excessive beta-adrenergic stimulation.