THE EFFECT OF ANTIHISTAMINICS, COCAINE AND RESERPINE ON AMINE-INDUCED RAT CARDIAC PHOSPHORYLASE ACTIVATION

¹ Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

Various compounds have been shown to potentiate certain of the effects of norepinephnine. The purpose of the present study was to determine whether compounds capable of potentiating responses to norepinephrine in other systems would also enhance the effect of this amine on rat cardiac phosphorylase a. Rats were pretreated with the agents under test and challenged with norepinephrine infusions. Phosphorylase was determined by the method of Diamond and Brody (1965). Tripelennamine, dexchlorpheniramine, promethazine, phenindamine and cocaine significantly enhanced norepinephrine-induced phosphorylase activation. Propranolol blocked this potentiation of the response to norepinephrine as well as the effect of norepinephnine alone. Triprolidine treatment or chronic administration of reserpine failed to influence norepinephnine-induced cardiac phosphorylase a levels,although the reserpine treatment reduced control values of the enzyme. Isoproterenol was a potent activator of cardiac phosphorylase; however, antihistamine or cocaine pretreatment did not enhance the isoproterenol response. It is concluded that compounds capable of blocking the uptake of norepinephrine by adrenergic neurons potentiate the effect of the amine on cardiac phosphorylase.