Arai Akira, Tomiyama Masahiko, Kannari Kazuya, Kimura Tamaki, Suzuki Chieko, Watanabe Mitsunori, Kawarabayashi Takeshi, Shen Huo, Shoji Mikio
Department of Neurology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
Synapse. 2008 Aug;62(8):632-5. doi: 10.1002/syn.20535.
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.
为了确定去甲肾上腺素转运体在多巴胺去神经支配的帕金森病纹状体中对左旋多巴衍生的细胞外多巴胺再摄取的作用，我们使用体内微透析技术，检测了接受左旋多巴（50mg/kg加12.5mg/kg苄丝肼）和左旋多巴加地昔帕明（25mg/kg，一种选择性去甲肾上腺素再摄取抑制剂）的6-羟基多巴胺损伤大鼠纹状体中的细胞外多巴胺水平。地昔帕明预处理增加了多巴胺去神经支配的纹状体中由左旋多巴衍生的细胞外多巴胺水平。本研究提供了证据，表明在多巴胺能去神经支配的纹状体中，左旋多巴衍生的多巴胺是通过去甲肾上腺素转运体而非多巴胺转运体被摄取的。这一结果表明，去甲肾上腺素转运体可能是帕金森病治疗中一个有前景的靶点。
