REGIONAL DISTRIBUTION AND METABOLISM OF H³-TYRAMINE IN THE RAT BRAIN

¹ New York University School of Medicine, Department of Psychiatry and Neurology, Neurochemistry Laboratory, New York, New York

The disposition and metabolism of H³-tyramine was investigated in different regions of the central nervous system after the intraventricular injection of the labeled amine. The hypothalamus contained the highest concentration of radioactive amines. The ratio of amines to acidic-neutral metabolites was higher in the hypothalamus than in other analyzed regions of the brain. In all analyzed regions of the central nervous system, with the exception of the striatum, the major part of the radioactivity of the amine fraction was associated with H³-octopamine. In the striatum all the radioactivity of the amine fraction was associated with unchanged H³-tyramine. The deaminated H³-metabolites of tyramine were isolated and identified in different regions of the brain. The major metabolite in all analyzed regions was found to be H³-p-hydroxyphenylacetic acid and the minor was found to be H³-p-hydroxyphenylethanol. Although both H³-phydroxyphenylacetic acid and H³-p-hydroxyphenylethanol were present in the conjugated form, the percentage of the latter in this form was greater. The ratio of conjugated to nonconjugated metabolites increased with time after administration of H³-tyramine. No evidence was obtained for the presence of deaminated metabolites from H³-octopamine newly formed from H³-tyramine. After inhibition of monoamine oxidase by pheniprazine there was a several-fold increase of the radioactivity in the H³-amine fraction concomitant with a decrease in the concentration of the deaminated H³-metabolites. Inhibition of dopamine--hydroxylase with disulfiram prevents the conversion of H³-tyramine to H³-octopamine, and after monoamine oxidase and dopamine--hydroxylase inhibition, H³-tyramine accumulates in all H³-octopamine-containing regions of the brain.