Glutamate receptor agonists up-regulate glutamate transporter GLAST in astrocytes

Glutamate receptor agonists up-regulate glutamate transporter GLAST in astrocytes
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DOI:
10.1097/00001756-199612200-00052
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发表时间:
1996-12-20
期刊:
影响因子:
1.7
通讯作者:
Schousboe, A
Schousboe, A
中科院分区:
医学4区
文献类型:
--
作者:
Gegelashvili, G;Civenni, G;Schousboe, A

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用L-谷氨酸(0.1-3 mM)长期处理原代培养的星形胶质细胞导致D-[H-3]天冬氨酸摄取量呈剂量依赖性增加。红藻氨酸/AMPA受体拮抗剂CNQX可消除这种作用,红藻氨酸可模拟这种作用,而AMPA或tACPD则不能。谷氨酸和红藻氨酸引起了显着的上调(82%和69%,分别)的GLAST,在培养的星形胶质细胞中的主要谷氨酸转运蛋白,虽然mRNA水平似乎不受影响。用dBcAMP长期处理培养物可刺激D-[H-3]天冬氨酸吸收以及GLAST表达。除了谷氨酸,没有使用的激动剂能够进一步增加的dBcAMP处理的星形胶质细胞的摄取能力。星形胶质细胞培养中谷氨酸转运的谷氨酸受体依赖性调节可能代表了脑中谷氨酸摄取的一种新的反馈调节机制。
LONG-TERM treatment of astrocytes in primary culture with L-glutamate (0.1-3 mM) resulted in a dose-dependent increase in D-[H-3]aspartate uptake. The effect was abolished by an antagonist of kainate/AMPA receptors, CNQX, and mimicked by kainate, but not by AMPA or tACPD. Both glutamate and kainate caused a dramatic up-regulation (82% and 69%, respectively) of GLAST, a predominant glutamate transporter in cultured astroglia, though the mRNA levels appeared unaffected. Long-term treatment of cultures with dBcAMP stimulated D-[H-3]aspartate uptake as well as GLAST expression. Apart from glutamate, none of the agonists used was capable of increasing further the uptake capacity of the dBcAMP-treated astroglia. The glutamate receptor-dependent modulation of glutamate transport in astroglial cultures may represent a novel feedback regulatory mechanism for glutamate uptake in the brain.