THE EFFECT OF VARIOUS DRUGS ON THE UPTAKE AND METABOLISM OF TYRAMINE-H³ IN THE RAT HEART

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

The uptake of tyramine-H³ and the subsequent formation and retention of octopamine-H³ were studied in vivo in the rat heart. A time-uptake study revealed that the amount of tyramine-H³ present in the heart was maximal 1 min after i.v. injection. Thereafter, the amount of tyramine-H³ decreased rapidly, while the amount of octopamine-H³ present increased with time. The amount of octopamine-H³ formed was proportional to the dose of labeled tyramine administered. Pretreatment with imipramine, tripelennamine, methylphenidate and amitriptyline significantly decreased the amount of tyramine-H³ present in the heart when tissue levels were measured at early times after amine injection. At 1 hr there was no significant difference in the tyramine-H³ content between control and drug-pretreated animals. The inhibition of tyramine-H³ uptake induced by the drugs was accompanied by a decrease in tissue octopamine-H³ levels. Promethazine pretreatment had no significant effect on either tyramine-H³ uptake or octopamine-H³ formation. The order of efficacy obtained with these drugs for the blockade of tyramine-H³ uptake correlated well with the ability of the compounds to block the uptake of norepinephrine and to inhibit the tyramine-induced increase in phosphorylase activity as previously reported. The data presented support the hypothesis that tyramine utilizes the same uptake system as does norepinephrine and that drugs which enhance the effects of norepinephrine and decrease the effects of tyramine do so by preventing the uptake of both amines.