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星形胶质细胞多巴胺转运由去甲肾上腺素转运体介导。

Astroglial dopamine transport is mediated by norepinephrine transporter.

作者信息

Takeda Hiroshi, Inazu Masato, Matsumiya Teruhiko

机构信息

Department of Pharmacology, and Intractable Diseases Research Center, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2002 Dec;366(6):620-3. doi: 10.1007/s00210-002-0640-0. Epub 2002 Sep 25.

Abstract

The aim of this study was to clarify the characteristics of the dopamine (DA) transport mechanism in cultured rat cortical astrocytes. Reverse transcription-polymerase chain reaction (RT-PCR) with DA transporter (DAT)-, norepinephrine (NE) transporter (NET)- and organic cation transporter 3 (OCT3)-specific primers demonstrated that rat cortical astrocytes and frontal cortex expressed DAT, NET and OCT3 mRNA. Specific [(3)H]DA and [(3)H]NE uptake were each partly inhibited by 1 micro M decynium 22, an extraneuronal monoamine transporter (EMT) and OCT inhibitor. The selective NE uptake inhibitor nisoxetine (0.1 micro M) and the tricyclic antidepressant desipramine (1 micro M) very potently inhibited the specific uptake of both [(3)H]DA and [(3)H]NE in astrocytes. In contrast, 0.1 micro M GBR-12935, a selective and potent DA uptake inhibitor, had no inhibitory activity on the uptake of either compound. These results suggest that cortical astrocytes regulate extracellular DA and NE concentrations through the uptake of DA and NE by the glial NET but not by DAT. Furthermore, an uptake(2) mechanism contributes to DA uptake in cortical astrocytes.

摘要

本研究的目的是阐明培养的大鼠皮质星形胶质细胞中多巴胺(DA)转运机制的特征。使用多巴胺转运体(DAT)、去甲肾上腺素(NE)转运体(NET)和有机阳离子转运体3(OCT3)特异性引物进行逆转录聚合酶链反应(RT-PCR),结果表明大鼠皮质星形胶质细胞和额叶皮质表达DAT、NET和OCT3 mRNA。特异性[³H]DA和[³H]NE摄取均部分受到1 μM癸鎓22(一种细胞外单胺转运体(EMT)和OCT抑制剂)的抑制。选择性NE摄取抑制剂尼索西汀(0.1 μM)和三环类抗抑郁药地昔帕明(1 μM)非常有效地抑制了星形胶质细胞中[³H]DA和[³H]NE的特异性摄取。相比之下,0.1 μM GBR-12935(一种选择性强效DA摄取抑制剂)对这两种化合物的摄取均无抑制活性。这些结果表明,皮质星形胶质细胞通过神经胶质NET而非DAT摄取DA和NE来调节细胞外DA和NE浓度。此外,一种摄取机制有助于皮质星形胶质细胞摄取DA。

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