Reuptake of L-DOPA-derived extracellular DA in the striatum of a rodent model of Parkinson's disease via norepinephrine transporter.

Akira Arai, Masahiko Tomiyama, Kazuya Kannari, Tamaki Kimura, Chieko Suzuki, Mitsunori Watanabe, Takeshi Kawarabayashi, Huo Shen, Mikio Shoji
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引用次数: 48

Abstract

To determine the role of norepinephrine transporter in reuptake of L-DOPA-derived extracellular DA in the DA-denervated Parkinsonian striatum, we examined extracellular DA levels in the striatum of 6-hydroxyDA-lesioned rats that received L-DOPA (50 mg/kg with 12.5 mg/kg of benserazide) and L-DOPA plus desipramine (25 mg/kg), a selective norepinephrine reuptake inhibitor, using in vivo microdialysis. The pretreatment with desipramine increased levels of extracellular DA derived from administrated L-DOPA in the DA-denervated striatum. This study provides evidence that L-DOPA-derived DA is taken up by the norepinephrine transporter, instead of the dopamine transporter, in the striatum with dopaminergic denervation. This result suggests that the norepinephrine transporter could be a promising target in the treatment for Parkinson's disease.

通过去甲肾上腺素转运体在帕金森病啮齿动物模型纹状体中再摄取左旋多巴衍生的细胞外DA。
为了确定去甲肾上腺素转运体在DA失神经帕金森纹状体中L-DOPA衍生的细胞外DA再摄取中的作用,我们使用体内微透析检测了6-羟多巴损伤大鼠纹状体中的细胞外DA水平,这些大鼠接受了L-DOPA (50 mg/kg加12.5 mg/kg苯拉西嗪)和L-DOPA加去西帕明(25 mg/kg),这是一种选择性去甲肾上腺素再摄取抑制剂。去西帕明预处理增加了DA去神经纹状体中由左旋多巴引起的细胞外DA水平。本研究证明,在多巴胺能失神经支配的纹状体中,左旋多巴衍生的DA是由去甲肾上腺素转运体而不是多巴胺转运体摄取的。这一结果表明,去甲肾上腺素转运蛋白可能是治疗帕金森病的一个有希望的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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