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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Benzodiazepines differently modulate EAAT1/GLAST and EAAT2/GLT1 glutamate transporters expressed in CHO cells.
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Benzodiazepines differently modulate EAAT1/GLAST and EAAT2/GLT1 glutamate transporters expressed in CHO cells.

机译：苯二氮卓类对CHO细胞中表达的EAAT1 / GLAST和EAAT2 / GLT1谷氨酸转运蛋白有不同的调节作用。

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摘要

It has been described recently that low concentrations of benzodiazepines stimulate the transport activity of the neuronal glutamate transporter EAAT3, whereas high concentrations inhibit it. The present study is aimed to investigate whether benzodiazepines have similar effects on the two glial glutamate transporter, EAAT1 and EAAT2. To this end, the transporters were transiently expressed in CHO cells and transport activity was determined by isotope fluxes using D-aspartate as non-metabolizable homologue of L-glutamate. At low D-aspartate concentrations (1 micromol/l) EAAT1-mediated uptake was reduced significantly by low concentrations of oxazepam (1 micromol/l) and diazepam (1 and 10 micromol/l). At 100 micromol/l D-aspartate oxazepam stimulated EAAT1-mediated uptake up to 150% in a dose dependent manner, whereas the inhibition by low concentrations of diazepam was attenuated. In contrast, a significant effect of diazepam on EAAT2-mediated uptake was only observed at 1000 micromol/l where uptake was inhibited by 60%. A similar inhibition was observed for EAAT1. These studies demonstrate a different modulation of EAAT1 and EAAT2 by benzodiazepines. Furthermore the glial transporters differ from the neuronal glutamate transporter. Thus, a complex in vivo response of the various transporters to benzodiazepines can be expected.
机译：最近已经描述了低浓度的苯二氮卓类刺激神经元谷氨酸转运蛋白EAAT3的转运活性，而高浓度抑制它。本研究旨在调查苯二氮卓类对两种神经胶质谷氨酸转运蛋白EAAT1和EAAT2是否具有相似的作用。为此，转运蛋白在CHO细胞中瞬时表达，并且使用D-天冬氨酸作为L-谷氨酸的不可代谢的同源物通过同位素通量确定转运活性。在低D-天门冬氨酸浓度（1微摩尔/升）下，低浓度的奥沙西m（1微摩尔/升）和地西m（1和10微摩尔/升）可显着降低EAAT1介导的摄取。在100μmol/ l的D-天冬氨酸奥沙西m刺激下，EAAT1介导的摄取以剂量依赖性方式达到150％，而低浓度地西az的抑制作用减弱。相比之下，地西对EAAT2介导的摄取的显著作用仅在1000微摩尔/升处被观察到，其中摄取被抑制60％。对于EAAT1，观察到类似的抑制作用。这些研究证明了苯二氮卓类化合物对EAAT1和EAAT2的不同调节。此外，神经胶质转运蛋白不同于神经元谷氨酸转运蛋白。因此，可以预期各种转运蛋白对苯并二氮杂卓的体内反应。

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