UPTAKE, RETENTION AND METABOLISM OF H³-TYRAMINE IN RAT ATRIA

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

Right atria from rats were incubated in Krebs-Ringer solution at 37°C for 20 minutes with H³-tyramine (1.4 x 10^-7 M). At the end of the incubation period, atria were washed with fresh Krebs-Ringer solution for periods up to 16 minutes. H³-tyramine rapidly disappeared from the atria during the first four minutes of the wash period. The rate of decrease of 113-tyramine slowed markedly during the remainder of the wash period. The disappearance of H³-tyramine during the wash period was accounted for by its quantitative conversion to H³-p-hydroxyphenylacetic acid. The amount of H³-octopamine remained constant throughout the wash period. Both desmethylimipramine (0.2-60 mg/kg i.p., 1 hour before sacrifice) and cocaine ( 10^-6-3 x 1O^-4 M, added to the incubation flask 15 minutes before the H³-tyramine) decreased the retention of H³-tyramine and the synthesis of H³-octopamine and H³-p-hydroxyphenylacetic acid. The inhibition of H³-octopamine synthesis produced by both drugs was competitive. No H³-p-hydroxymandelic acid was synthesized by intact atria either in control experiments or in the presence of drugs. In addition, no H³-octopamine was detected in bathing or wash solutions at any time. These results indicate there are two intraneuronal pools of H³-tyramine within the atria: one which turns over rapidly and is converted to H³-p-hydroxy-phenylacetic acid and one which remains firmly bound within the atria. H³-octopamine is retained in a site which is inaccessible to intraneuronal monoamine oxidase. Both desmethylimipramine and cocaine competitively inhibit the neuronal uptake of H³-tyramine into adrenergic neurons of the atria.