Interaction of amrinone with endogenous adenosine in guinea-pig atria.
In spontaneously beating atria from reserpine-treated guinea-pigs, amrinone (10 microM 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. 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. Cumulative concentrations of amrinone (1 mM) antagonized the reduction of rate of contraction and amplitude induced by dipyridamole 1 microM in spontaneously beating atria and restored the maximum contractile effect reached in the absence of dipyridamole. In spontaneously beating preparations incubated in the presence of adenosine deaminase (1 u 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. Adenosine at 0.1 microM and 0.5 microM 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.
Dorigo
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P
Maragno
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D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000243:Adenosine Deaminase / Q000378:metabolism; D000631:Aminopyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000676:Amrinone; D000818:Animals; D002301:Cardiac Glycosides / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004176:Dipyridamole / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D000631:Aminopyridines; D002301:Cardiac Glycosides; D002316:Cardiotonic Agents; D004176:Dipyridamole; D012110:Reserpine; D013806:Theophylline; C028322:8-phenyltheophylline; D000243:Adenosine Deaminase; D000676:Amrinone; D000241:Adenosine