THE EFFECT OF TYRAMINE, AMPHETAMINE AND METARAMINOL ON THE METABOLIC DISPOSITION OF ³H-NOREPINEPHRINE RELEASED FROM THE ADRENERGIC NEURON

¹ Laboratory of Chemical Pharmacology, National Heart institute, National institutes of Health, Bethesda, Maryland

The mechanism by which tyramine, amphetamine and metaraminol alter the distribution of ³H-norepinephrine (NE) and its ³H-metabolites released in the effluent of the perfused rat heart was studied. In hearts in which NE stores were previously labeled by perfusion with dl-³H-NE, the distribution of ³H-metabolites in the effluent during the control period was as follows: ³H-NE, 4%; ³H-normetanephrine, 12%; ³H-O-methylated deaminated products (OMDA), 49%; and ³H-catechol deaminated products (CDA), 35%. When tyramine or amphetamine was perfused at concentrations which did not increase the efflux rate of total tritium the ³H-NE content of the perfusate was increased more than 10 times and the ³H-deaminated products (³H-OMDA + ³H-CDA) were proportionally reduced. Perfusion with media containing Ro 4-1284, a benzoquinolizine derivative with a reserpine-like action, doubled the rate of efflux of tritium with deaminated products (³H-OMDA + ³H-CDA) accounting for more than 90% of total tritium released. During perfusion with Ro 4-1284 the addition of tyramine, amphetamine, metaraminol or tranylcypromine (a monoamine oxidase (MAO) inhibitor) increased the ³H-NE content of the perfusate up to 6-fold without increasing total tritium efflux. The ability of each sympathomimetic amine to increase the outflow of ³H-NE from the perfused heart was found to correlate roughly with its ability to inhibit MAO activity in vitro in a homogenate of heart. It is concluded that tyramine, amphetamine and metaraminol release ³H-NE as the free amine because they can protect unbound cytoplasmic ³H-NE from oxidation by MAO.