Interaction of amrinone with endogenous adenosine in guinea‐pig atria

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Abstract
1 In spontaneously beating atria from reserpine-treated guinea-pigs, amrinone (10 μm to 2 mm) 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 mm) antagonized the reduction of rate of contraction and amplitude induced by dipyridamole 1 μm 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 mm thus indicating their cholinergic nature. 5 Adenosine at 0.1 μm and 0.5 μm significantly inhibited the inotropic effect induced by amrinone (0.03 to 3 mm) 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.