Cysteinyl leukotriene receptor 1 is involved in N-methyl-D-aspartate-mediated neuronal injury in mice  

作　　者：Qian DING Er-qing WEI Yan-jun ZHANG Wei-ping ZHANG Zhong CHEN 

机构地区：[1]Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China

出　　处：《Acta Pharmacologica Sinica》2006年第12期1526-1536,共11页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China(№30371637).

摘　　要：Aim： To determine whether cysteinyl leukotriene receptor 1 （CysLT1 receptor） is involved in N-methyl-D-aspartate （NMDA）-induced excitotoxic injury in the mouse brain. Methods： Brain injury was induced by NMDA microinjection （50-150 nmol in 0.5 μL） into the cerebral cortex. The changes in CysLT1 receptor expression 24 h after NMDA injection and the effects of a CysLT1 receptor antagonist, pranlukast （0.01 and 0.1 mg/kg）, an NMDA receptor antagonist, ketamine （30 mg/kg）, and an antioxidant, edaravone （9 mg/kg） were observed. Results： In the NMDA-injured brain, the CysLT1 receptor mRNA, and protein expression were upregulated, and the receptor was mainly localized in the neurons and not in the astrocytes. Pranlukast, ketamine and edaravone decreased NMDA-induced injury; pranlukast （0.1 mg/kg） and ketamine inhibited the upregulated expression of the CysLT1 receptor. Conclusion： CysLT1 receptor expression in neurons is upregulated after NMDA injection, and NMDA-induced responses are inhibited by CysLT1 receptor antagonists, indicating that the increased CysLT1 receptor is involved in NMDA excitotoxicity.Aim： To determine whether cysteinyl leukotriene receptor 1 （CysLT1 receptor） is involved in N-methyl-D-aspartate （NMDA）-induced excitotoxic injury in the mouse brain. Methods： Brain injury was induced by NMDA microinjection （50-150 nmol in 0.5 μL） into the cerebral cortex. The changes in CysLT1 receptor expression 24 h after NMDA injection and the effects of a CysLT1 receptor antagonist, pranlukast （0.01 and 0.1 mg/kg）, an NMDA receptor antagonist, ketamine （30 mg/kg）, and an antioxidant, edaravone （9 mg/kg） were observed. Results： In the NMDA-injured brain, the CysLT1 receptor mRNA, and protein expression were upregulated, and the receptor was mainly localized in the neurons and not in the astrocytes. Pranlukast, ketamine and edaravone decreased NMDA-induced injury; pranlukast （0.1 mg/kg） and ketamine inhibited the upregulated expression of the CysLT1 receptor. Conclusion： CysLT1 receptor expression in neurons is upregulated after NMDA injection, and NMDA-induced responses are inhibited by CysLT1 receptor antagonists, indicating that the increased CysLT1 receptor is involved in NMDA excitotoxicity.

关 键 词：cysteinyl leukotriene receptor EXCITOTOXICITY N-METHYL-D-ASPARTATE leukotriene receptor antagonist PRANLUKAST NMDA receptor antagonist KETAMINE 

分 类 号：R74[医药卫生—神经病学与精神病学]