THE EFFECT OF l‐DOPA AND AN INHIBITOR OF PERIPHERAL DECARBOXYLATION ON GLUCOSE METABOLISM IN BRAIN1

Abstract

Abstract– The effect of the administration of l‐DOPA plus an inhibitor of peripheral l‐aromatic amino acid decarboxylase (aromatic‐l‐amino‐acid carboxy‐lyase; EC 4.1.1.28) on the metabolism of glucose in brain was studied by administering [U‐I4C]glucose (20μCi) to three groups of rats: (1) rats that had been injected with l‐DOPA (200mg/kg) 28min earlier; (2) rats that had been similarly injected with l‐DOPA and also with N‐(d,l‐seryl)‐N′‐(2,3,4‐trihydroxybenzyl)hydrazine (50 mg/kg), an inhibitor of l‐aromatic amino acid decarboxylase, 30min before the l‐DOPA; and (3) appropriate controls. The flux of 14C from glucose in plasma to those amino acids that are in equilibrium with the tricarboxylic acid cycle intermediates was reduced by treatment with l‐DOPA and reduced further by treatment with l‐DOPA and the decarboxylase inhibitor. Concentrations of glucose in brain and in plasma were increased after treatment with l‐DOPA; these increases were attenuated if the inhibitor was given before the l‐DOPA. After treatment with l‐DOPA, there were decreases in the concentration of aspartate, tryptophan, and tyrosine in brain. After the administration of l‐DOPA and the decarboxylase inhibitor, the concentrations in brain of alanine, glutamate, tyrosine, and phenylalanine were greater, and the concentrations of aspartate, leucine, lysine, histidine, arginine, and tryptophan were less than in control rats.