Interaction of amrinone with endogenous adenosine in guinea‐pig atria

1 In spontaneously beating atria from reserpine‐treated guinea‐pigs, amrinone (10 μ m to 2 m m ) induced a positive inotropic and chronotropic effect that was preceded by a transient reduction in contractile force and in frequency. Both the positive and negative effects were concentration‐dependent. 2 The inotropic action of amrinone was antagonized by low concentrations of 8‐phenyltheophylline that compete with adenosine at R‐receptors on plasma membrane without significantly influencing phosphodiesterase activity. 3 Cumulative concentrations of amrinone (1 m m ) antagonized the reduction of rate of contraction and amplitude induced by dipyridamole 1 μ m in spontaneously beating atria and restored the maximum contractile effect reached in the absence of dipyridamole. 4 In spontaneously beating preparations incubated in the presence of adenosine deaminase (1u ml −1 ), amrinone lost its positive effects on the atria and only reduction of rate and contractile force was evident. Both effects were antagonized by scopolamine 1 m m thus indicating their cholinergic nature. 5 Adenosine at 0.1 μ m and 0.5 μ m significantly inhibited the inotropic effect induced by amrinone (0.03 to 3 m m ) and the concentration‐effect curves of amrinone obtained in the absence and presence of adenosine clearly indicate a competitive antagonism between the two drugs. Thus the contractile activity of amrinone in spontaneously beating atria from reserpine‐treated guinea‐pigs originates from a displacement of adenosine from its R‐receptor sites in the cardiac cell.