A novel glycine site-specific N-methyl-D-aspartate receptor antagonist prevents activation of the NMDA/NO/CGMP pathway by ammonia

被引：24

作者：

Hilgier, W

Oja, SS

Saransaari, P

Albrechta, J

机构：

[1] Polish Acad Sci, Med Res Ctr, Dept Neurotoxicol, PL-02106 Warsaw, Poland

[2] Tampere Univ, Sch Med, Brain Res Ctr, FIN-33101 Tampere, Finland

[3] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland

来源：

BRAIN RESEARCH | 2004年 / 1015卷 / 1-2期

基金：

芬兰科学院;

关键词：

striatum; microdialysis; ammonia; cGMP; NMDA receptor; glycine site;

D O I：

10.1016/j.brainres.2004.05.014

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Intrastriatal administration of ammonium ions ("ammonia") via a microdialysis probe overactivates N-methyl-D-aspartate (NMDA) receptors, which results in cGMP accumulation in the microdialysates. Co-administration of a potent glycine site-specific NMDA receptor antagonist CGP 78608 ([(1S)-1-[[(7-bromo-1,2,3,4-tetrahydro-2,3-dioxo-5-quinoxalinyl)methyl] amino] ethyl] phosphonate) significantly reduced (at 20 nM) or abolished (at 100 nM) ammonia-dependent cGMP synthesis. Since NMDA receptor activation is an important causative factor in ammonia neurotoxicity, the present results suggest the glycine site of the receptor to be a potential valuable target for protective intervention. (C) 2004 Elsevier B.V. All rights reserved.

引用

页码：186 / 188

页数：3

共 14 条

[1] Synthesis, radiolabelling and biological characterization of (D)-7-iodo-N-(1-phosphonoethyl)-5-aminomethylquinoxaline-2,3-dione, a glycine-binding site antagonist of NMDA receptors [J].