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谷氨酸和MK-801对正常和帕金森模型大鼠纹状体内多巴胺代谢的影响

段春礼, 孙晓红, 姬曼, 杨慧

首都医科大学神经科学研究所, 北京神经修复重点实验室.北京 100054

摘要

采用微透析和高效液相色谱-电化学 (HPLC-ECD)技术研究了谷氨酸和MK-801对正常和帕金森模型大鼠纹状体内多巴胺代谢的影响。用微透析的方法在大鼠纹状体内分别定位给以左旋多巴、L-谷氨酸和/或MK-801，同时收集透析液，用HPLC-ECD方法测定透析液中多巴胺代谢产物的浓度. 微透析和HPLC-ECD分析结果表明:纹状体内定位给以左旋多巴，正常大鼠和帕金森模型大鼠纹状体内多巴胺代谢产物的浓度均升高； 纹状体内定位给以L-谷氨酸，可使正常大鼠纹状体内多巴胺代谢产物的浓度降低，但对帕金森大鼠模型纹状体内多巴胺代谢产物浓度的降低不显著；纹状体内定位给以MK-801，正常大鼠纹状体内多巴胺代谢产物的浓度升高；但对帕金森大鼠模型纹状体内多巴胺代谢产物浓度的升高不显著；纹状体内同时定位给以MK-801和L-谷氨酸可以有效防止L-谷氨酸所致正常大鼠纹状体内多巴胺代谢产物浓度的降低。结果提示，谷氨酸可以通过NMDA受体调节多巴胺的代谢。尽管非竞争性NMDA拮抗剂—MK-801可以有效防止L-谷氨酸所致正常大鼠纹状体内多巴胺代谢产物浓度的降低，但却不能有效地改善帕金森大鼠模型纹状体内多巴胺的代谢水平。 因此正常及帕金森病情况下谷氨酸-多巴胺相互作用机制和MK-801改善PD症状的机制还有待进一步研究。

关键词： 帕金森病; 微透析; 大鼠; 谷氨酸; MK-801; 3,4-二羟基苯乙酸; 高香草酸

Effects of glutamate and MK-801 on the metabolism of dopamine in the striatum of normal and parkinsonian rats

Duan Chunli, Sun Xiaohong, Ji Man, Yang Hui

Beijing Institute for Neurosciences, Beijing Center for Neural Regeneration and Repairing, Capital University of Medical Science.Beijing 100054

Abstract

The direct effects of glutamate and dizocilpine maleate (MK-801, non-competitive N-Methyl-d-aspartate glutamate receptor antagonist) on the metabolism of dopamine were investigated in striatum of normal and parkinsonian rats. L-dopa, L-glutamic acid and MK-801 were administered in the striatum locally by microdialysis. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were simultaneously sampled by microdialysis. The concentrations of DOPAC and HVA were assayed by high performance liquid chromatography with electrochemical detection (HPLC-ECD). L-dopa increased the concentrations of DOPAC and HVA in the striatum of normal and the parkinsonian rats. L-glutamic acid decreased the concentrations of DOPAC and HVA in striatum of normal rats but not the parkinsonian rats. MK-801 increased the concentrations of DOPAC and HVA in the striatum of normal rats but not the parkinsonian rats. MK-801 prevented the decrease of DOPAC and HVA in the striatum of normal rats. Our results indicate that glutamate modulates the metabolism of DA through NMDA receptors and that the improvement of PD by MK-801 is not through improving the metabolism of DA.

Key words: Parkinson's disease;Microdialysis;Rat;Glutamate;Dizocilpine Maleate;3,4-Dihydroxyphenylacetic Acid;Homovanillic acid

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引用本文：

段春礼, 孙晓红, 姬曼, 杨慧. 谷氨酸和MK-801对正常和帕金森模型大鼠纹状体内多巴胺代谢的影响[J]. 生理学报 2005; 57 (1): .

Duan Chunli, Sun Xiaohong, Ji Man, Yang Hui. Effects of glutamate and MK-801 on the metabolism of dopamine in the striatum of normal and parkinsonian rats. Acta Physiol Sin 2005; 57 (1): (in Chinese with English abstract).