Pathways linking L-phenylalanine and 2-phenylethylamine with p-tyramine in rabbit brain.

Concentrations of labeled p-tyramine and 2-phenylethylamine were measured in rabbit brain 10 min after the intraventricular administration of either radioactive amine. In both cases the recoveries of the newly synthesized amine and of the unchanged precursor were significantly increased in animals pretreated with the monoamine oxidase inhibitor pargyline. Significant amounts of both amines were present in rabbit brain 10 min after the intraventricular injection of labeled L-phenylalanine. Pretreatment with pargyline increased their recoveries, whereas alpha-methyldopa (an L-aromatic amino acid decarboxylase enzyme inhibitor, L-AAADI) decreased them considerably, and no significant alteration was found in L-alpha-methyldopa hydrazine (a peripheral L-AAADI) pretreated animals. These results provide evidence for a new biochemical pathway in brain for p-tyramine biosynthesis, with L-phenylalanine (bypassing the formation of L-tyrosine) or 2-phenylethylamine as precursors. The significance and implications of these metabolic routes are discussed, especially considering that p-tyramine itself can be converted to catecholamines.