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.
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007980:Levodopa / Q000494:pharmacology; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism; D013997:Time Factors
D002395:Catecholamines; D007980:Levodopa; C017342:gamma-glutamyl DOPA; D004295:Dihydroxyphenylalanine; D001142:Aromatic-L-Amino-Acid Decarboxylases; C001746:3-methoxytyramine; D004298:Dopamine; D009638:Norepinephrine