FACTORS INFLUENCING THE DEPLETION OF CARDIAC NOREPINEPHRINE BY TYRAMINE

¹ Department of Pharmacology, College of Medicine, Howard University, Washington, D.C.

Tyramine (20-500 mg/kg i.m.) depleted 30% of the cardiac catecholamines during the first 30 mm, regardless of the dose employed. However, the degree of depletion increased to 50% when monoamine oxidase was inhibited by prior treatment of the animals with pheniprazine or pargyline. When adequate levels of tyramine were maintained by administering either a large single dose or small repeated doses, this amine depleted almost 80% of the cardiac catecholamines at 2 hr after administration. Inhibition of dopamine -hydroxylase by disulfiram failed to influence the rate of tyramine-induced depletion. Octopamine (20-50 mg/kg i.m.) caused the same degree of depletion as 20 mg/kg of tyramine. In animals pretreated with reserpine 96, 120, 144, 178, 192 and 240 hr prior to the experiment, tyramine caused the same degree of depletion of cardiac catecholamines as in the normal rats. The pattern of subcellular distribution of cardiac catecholamines after reserpine appeared to be unaltered. Thus it appears that the pharmacologic actions of tyramine result primarily from the direct action of this monoamine and not from that of its -hydroxylated derivative. The depletion by tyramine depends on maintaining the concentration of this amine in the heart. Recovery from reserpine depletion proceeds with a gradual increase in the number of norepinephrine binding sites, each with a normal affinity for norepinephrine.