通过全身给予γ-谷氨酰-L-3,4-二羟基苯丙氨酸增加小鼠脑中的儿茶酚胺。

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

作者信息

Ichinose H, Togari A, Suzuki H, Kumagai H, Nagatsu T

出版信息

J Neurochem. 1987 Sep;49(3):928-32. doi: 10.1111/j.1471-4159.1987.tb00982.x.

DOI:10.1111/j.1471-4159.1987.tb00982.x

Abstract

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.

摘要

我们研究了全身给予γ-谷氨酰-L-3,4-二羟基苯丙氨酸（γ-Glu-DOPA）对脑内儿茶酚胺含量的影响。γ-Glu-DOPA在体外通过γ-谷氨酰转肽酶和芳香族L-氨基酸脱羧酶的相继作用，与脑匀浆一起转化为多巴胺（DA）。给小鼠腹腔注射γ-Glu-DOPA后，脑内DA显著增加，去甲肾上腺素（NA）适度增加。内源性DA增加后，主要DA代谢产物（3,4-二羟基苯乙酸和高香草酸）升高。这些增加呈剂量依赖性。给予γ-Glu-DOPA后30分钟内观察到DA的最大升高，但给药后2小时观察到NA的显著增加。这些结果表明γ-Glu-DOPA可能适用于帕金森病的治疗。