ADMINISTRATION OF L-3,4-DIHYDROXYPHENYLALANINE TO RATS AFTER COMPLETE HEPATECTOMY .1. METABOLITES IN TISSUES

14C-Labeled l-3,4-dihydroxyphenylalanine (l-DOPA, 20 μCi, 11 mg/kg) was injected intravenously into control rats and into rats after complete hepatectomy. The rats were killed after 20 min, and studies were made of the disposition and metabolism of the l-[14C]DOPA in plasma, erythrocytes, brain, heart, kidney, gastrointestinal tract, spleen, lung, adrenals, muscle, pancreas and liver (of the controls). Total 14C in these tissues accounted for 31 per cent of the dose in control rats and 53 per cent of the dose in the operated animals. The tissues of the hepatectomized rats that contained a disproportionately high amount of radioactivity were kidney, spleen, lung, heart and erythrocytes. Amounts of [14C]dopamine higher than in control animals were found in most tissues of the hepatectomized rats and especially in the kidneys, although there was evidence that decarboxylation of DOPA was inhibited in the operated animals. Further metabolism to norepinephrine was limited in most tissues of the hepatectomized rats; most of the radioactivity was associated with 3,4-dihydroxyphenylacetic acid. This suggests that after hepatectomy there is an impairment of vesicular uptake or of retention of dopamine or an inhibition of β-hydroxylation. As a result, most of the dopamine that is formed is metabolized by mitochondrial monoamine oxidase [amine oxidase (flavincontaining) EC 1.4.3.4] to form 3,4-dihydroxyphenylacetic acid. There was little evidence that monoamine oxidase was inhibited in the hepatectomized animals. © 1979.