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培高利特对大鼠纹状体内源性和外源性左旋多巴代谢的影响:一项微透析研究。

Effect of pergolide on endogenous and exogenous L-DOPA metabolism in the rat striatum: a microdialysis study.

作者信息

Dethy S, Laute M A, Luxen A, Hildebrand J, Goldman S

机构信息

Service de Neurologie, ULB-Hôpital Erasme, Brussels, Belgium.

出版信息

J Neural Transm Gen Sect. 1995;101(1-3):1-11. doi: 10.1007/BF01271541.

Abstract

We used a model of intrastriatal microdialysis in freely moving rats to study the effect of pergolide, a mixed D1/D2 dopamine (DA) receptor agonist with predominant D2 action in vivo, on the biotransformation of endogenous and exogenous L-DOPA. Levels of L-DOPA, DA, DOPAC, HVA and 5-HIAA were measured by high performance liquid chromatography. Pergolide (50 micrograms/kg, i.p.) caused a 47%, 65% and 70% decrease in basal striatal extracellular (EC) levels of DOPAC, HVA and DA, respectively. L-DOPA (100 mg/kg, i.p.), injected 2 hours after carbidopa, produced significant increase in EC levels of L-DOPA, DOPAC, HVA and DA in rats with and without local perfusion of 10(-4) M pergolide. The DOPAC peak value was lower and was reached 60 minutes later in the group with pergolide. This study demonstrated inhibitory effects of pergolide on endogenous DA release and influence of pergolide on exogenous L-DOPA biotransformation.

摘要

我们采用自由活动大鼠纹状体内微透析模型,研究培高利特(一种在体内主要作用于D2的D1/D2多巴胺(DA)受体混合型激动剂)对内源性和外源性左旋多巴生物转化的影响。通过高效液相色谱法测定左旋多巴、多巴胺、3,4-二羟基苯乙酸(DOPAC)、高香草酸(HVA)和5-羟吲哚乙酸(5-HIAA)的水平。培高利特(50微克/千克,腹腔注射)使纹状体细胞外(EC)基础水平的DOPAC、HVA和DA分别降低47%、65%和70%。在给予卡比多巴2小时后注射左旋多巴(100毫克/千克,腹腔注射),无论是否局部灌注10^(-4) M培高利特,大鼠纹状体细胞外液中左旋多巴、DOPAC、HVA和DA的水平均显著升高。在培高利特组中,DOPAC峰值较低且延迟60分钟出现。本研究证明了培高利特对内源性多巴胺释放的抑制作用以及对外源性左旋多巴生物转化的影响。

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