Increase of catecholamines in mouse brain by systemic administration of gamma-glutamyl L-3,4-dihydroxyphenylalanine.

We investigated the effect of systemic administration of gamma-glutamyl L-3,4-dihydroxyphenylalanine (gamma-Glu-DOPA) on catecholamine contents in the brain. gamma-Glu-DOPA was transformed to dopamine (DA) in vitro with brain homogenate by the sequential action of gamma-glutamyl transpeptidase and aromatic L-amino acid decarboxylase. Intraperitoneal injection of gamma-Glu-DOPA to mice increased DA markedly and noradrenaline (NA) moderately in the brain. The increase of endogenous DA was followed by elevation of the main DA metabolites (3,4-dihydroxyphenyl-acetic acid and homovanillic acid). These increases were in a dose-dependent manner. The maximal elevation of DA was observed within 30 min after administration of gamma-Glu-DOPA, but a substantial increase of NA was observed 2 h after the administration. These results suggest that gamma-Glu-DOPA may be applicable to the treatment of Parkinson's disease.