Phosphinothricin induces epileptic activity via nitric oxide production through NMDA receptor activation in adult mice

被引：38

作者：

Lapouble, E ^{[1
]}

Montécot, C ^{[1
]}

Sevestre, A ^{[1
]}

Pichon, J ^{[1
]}

机构：

[1] Univ Orleans, Lab Metab Cerebral & Neuropathol, UPRES 2633, F-45067 Orleans 2, France

来源：

BRAIN RESEARCH | 2002年 / 957卷 / 01期

关键词：

phosphinothricin; glutamine synthetase; N-methyl-D-aspartate; nitric oxide synthase; electroencephalogram; behavior; herbicide;

D O I：

10.1016/S0006-8993(02)03597-7

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Phosphinothricin (PPT), the active component of a widely used herbicide, induces convulsions in rodents and humans. PPT shares structural analogy with glutamate, which could explain its powerful inhibitory effect on glutamine synthetase and its probable binding to glutamate receptors. To characterize the epileptogenic effect of PPT, electrographic and behavioural studies were carried out on PPT-treated adult mice. We investigated the role of N-methyl-D-aspartate (NMDA) receptor activation and nitric oxide (NO) production in induction of seizures triggered by PPT, by using specific NMDA antagonist and nitric oxide synthase (NOS) inhibitor. The inhibitory effect of PPT on glutamine synthetase of mouse brain was assessed after in vitro and in vivo treatments. The results obtained show that PPT induces tonic-clonic seizures and generalized convulsions in mice. They suggest that these seizures are mediated through an NMDA receptor activation and NO production, without involvement of inhibition of glutamine synthetase. (C) 2002 Elsevier Science B.V. All rights reserved.

引用

页码：46 / 52

页数：7

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