Stimulation of prostaglandin E2-EP3 receptors exacerbates stroke and excitotoxic injury

被引：42

作者：

Ahmad, Muzamil

Ahmad, Abdullah Shafique

Zhuang, Hean

Maruyama, Takayuki

Narumiya, Shuh

Dore, Sylvain

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Anesthesiol Crit Care Med, Dept Neurosci, Baltimore, MD 21205 USA

[2] Ono Pharmaceut Co Ltd, Discovery Res Inst 1, Osaka, Japan

[3] Kyoto Univ, Fac Med, Dept Pharmacol, Kyoto 6068501, Japan

来源：

JOURNAL OF NEUROIMMUNOLOGY | 2007年 / 184卷 / 1-2期

关键词：

cerebral ischemia; EP3 receptor agonist; G-protein-coupled receptors; neurotoxicity; NMDA;

D O I：

10.1016/j.jneuroim.2006.12.012

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The effect of PGE(2) EP3 receptors on injury size was investigated following cerebral ischemia and induced excitotoxicity in mice. Treatment with the selective EP3 agonist ONO-AE-248 significantly and dose-dependently increased infarct size in the middle cerebral artery occlusion model. In a separate experiment, pretreatment with ONO-AE-248 exacerbated the lesion caused by N-methyl-D-aspartic acid-induced acute excitotoxicity. Conversely, genetic deletion of EP3 provided protection against N-methyl-D-aspartic acid-induced toxicity. The results suggest that PGE(2), by stimulating EP3 receptors, can contribute to the toxicity associated with cyclooxygenase and that antagonizing this receptor could be used therapeutically to protect against stroke- and excitotoxicity-induced brain damage. (c) 2007 Elsevier B.V. All rights reserved.

引用

页码：172 / 179

页数：8

共 52 条

[31] PROSTAGLANDIN-SYNTHASE-2 GENE DISRUPTION CAUSES SEVERE RENAL PATHOLOGY IN THE MOUSE [J].