THE EFFECT OF THEOPHYLLINE ON AMINE-INDUCED CARDIAC PHOSPHORYLASE ACTIVATION AND CARDIAC CONTRACTILITY

¹ Department of Pharmacology, Michigan State University, East Lansing, Michigan

Theophylline in doses greater than 25 mg/kg potentiated the effect of norepinephrine, tyramine and isoproterenol on cardiac phosphorylase a in the intact rat. Theophylline also shifted to the left the dose-response curve obtained with norepinephrine in animals pretreated with tripelennamine. Theophylline alone caused a small but significant rise in cardiac phosphorylase a which was prevented by reserpine or propranolol pretreatment. Doses of theophylline which enhanced the phosphorylase-activating effect of the amines were found to be cardiodepressant and decreased rather than potentiated the positive inotropic effect of norepinephrine in open-chest rats. It is concluded that the phosphodiesterase inhibition produced by theophylline, although perhaps responsible for the potentiation of amines, is not related to the increase in cardiac contractility produced by the drug. The effects of theophylline on cardiac contractility and the interaction of the drug with the adrenergic amines may better be explained on the known effects of the methyl xanthines on intracellular calcium levels.

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