OXYGEN FREE-RADICALS REGULATE NMDA RECEPTOR FUNCTION VIA A REDOX MODULATORY SITE

被引：183

作者：

AIZENMAN, E ^{[1
]}

HARTNETT, KA ^{[1
]}

REYNOLDS, IJ ^{[1
]}

机构：

[1] UNIV PITTSBURGH,SCH MED,DEPT PHARMACOL,PITTSBURGH,PA 15261

来源：

NEURON | 1990年 / 5卷 / 06期

关键词：

D O I：

10.1016/0896-6273(90)90343-E

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

A nobel modulatory site on the N-methyl-D-aspartate (NMDA) receptor that is sensitive to sulfhydryl redox reagents was recently described. Here we report that this redox modulatory site is susceptible to oxidation by reactive oxygen species endogenous to the CNS. Oxygen free radicals generated by xanthine and xanthine oxidase were observed to decrease NMDA-induced changes in intracellular free Ca2+ concentrations and NMDA-evoked cation currents in cortical neurons in culture. Additionally, a sublethal production of free radicals by xanthine and xanthine oxidase reversed a dithiothreitol-induced enhancement of NMDA-mediated neurotoxicity in vitro. These results show that NMDA receptor function is modulated at its redox site by endogenous substances that normally accompany tissue reperfusion following an ischemic event. This novel mechanism for NMDA receptor regulation may have profound implications in the outcome of glutamate neurotoxicity in vivo.

引用

页码：841 / 846

页数：6

共 36 条

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