Effect of dihydroxyphenylalanine administered with a monoamine oxidase inhibitor on glucose metabolism in rat brain

Abstract

Injection of l-3,4-dihydroxyphenylalanine ( l-dopa) without and with an inhibitor (β-phenylisopropylhydrazine; JB516) of the enzyme, EC 1.4.3.4 monoamine: oxygen oxidoreductase (deaminating), induced hyperglycemia in fed, but not in fasted, rats. The rates of entry into and of removal of glucose from the glucose space were higher in fed rats treated with l-dopa and JB516 than in control rats. Thus, uptake of glucose by peripheral tissues is increased after treatment with l-dopa and JB516. Concentrations of glucose in brain were higher in rats treated with l-dopa and JB516 than in control rats, but uptakes of glucose- 14C by brain were not meaningfully different in controls and treated rats. At 15 min after a pulse injection of glucose- 14C, flux of 14C into lactate and alanine in brain was the same in control rats as in rats treated with l-dopa and JB516; the flux of 14C into glutamate, glutamine, aspartate, and γ-aminobutyric acid was markedly decreased in the treated rats. It is concluded that dopa injected after a monoamine oxidase inhibitor inhibits the metabolism, in brain, of glucose to the tricarboxylic acid cycle intermediates. The accumulation of unmetabolized glucose in brain in the treated rats suggests a second point of inhibition, possibly at the formation of glucose 6-phosphate.