Phenylethanolamines inhibit NMDA receptors by enhancing proton inhibition

被引：185

作者：

Mott, DD ^{[1
]}

Doherty, JJ ^{[1
]}

Zhang, SN ^{[1
]}

Washburn, MS ^{[1
]}

Fendley, MJ ^{[1
]}

Lyuboslavsky, P ^{[1
]}

Traynelis, SF ^{[1
]}

Dingledine, R ^{[1
]}

机构：

[1] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA

来源：

NATURE NEUROSCIENCE | 1998年 / 1卷 / 08期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/3661

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The phenylethanolamines, ifenprodil and CP-101,606, are NMDA receptor antagonists with promising neuroprotective properties. In recombinant NMDA receptors expressed in Xenopus oocytes, we found that these drugs inhibit NMDA receptors through a unique mechanism, making the receptor more sensitive to inhibition by protons, an endogenous negative modulator. These findings support a critical role for the proton sensor in gating the NMDA receptor and point the way to identifying a context-dependent NMDA receptor antagonist that is inactive at physiological pH, but is a potent inhibitor during the acidic conditions that arise during epilepsy, ischemia and brain trauma.

引用

页码：659 / 667

页数：9

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