THE INFLUENCE OF ENZYME INHIBITORS ON THE ACTION OF EPINEPHRINE ON THE FROG'S HEART

¹ Department of Pharmacology, Temple University School of Medicine, Philadelphia 40, Pa.

1. Blockade of aerobic metabolism by anaerobic conditions, cyanide, or azide, or blockade of the Krebs tricarhoxylic cycle with fluoroacetate influenced the positive inotropic action of epinephrine on the frog's heart. Since the presence of an anaerobic source of energy in the form of glucose allowed an essentially normal response to epinephrine in the presence of the above conditions of limited metabolism, it has been concluded that this action of epinephrine is not dependent upon the functioning of either the cytochrome system or the tricarboxylic acid cycle.

2. Blockade of glycolysis by iodoacetate or iodoacetamide so that anaerobic function of the frog's heart was no longer possible did not affect the positive inotropic action of epinephrine on the aerobically beating heart. These results minimize the importance of the energy arising from the glycolytic system for this action of epinephrine. The reason for previous contrary conclusion has been suggested.

3. Moderate concentrations of 2,4-dinitrophenol interfered with the action of epinephrine. The locus of action of epinephrine indicated by these findings is between the metabolically formed high-energy phosphate and the contractile process.