期刊
NEUROCHEMISTRY INTERNATIONAL
卷 56, 期 4, 页码 535-545出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2009.12.016
关键词
mGluR1; mGluR5; NMDA receptor; Neuronal nitric oxide synthase; cGMP; Akt
资金
- Ministerio de Ciencia e Innovacion [SAF2005-06089, SAF2008-00062, CSD2008-00005]
- Conselleria de Educacion [ACOMP06/005, ACOMP-2009-025, Prometeo/2009/027]
- Conselleria de Sanitat of Generalitat Valenciana [AP005/06, EVES 034/2007, AP-024/08, A-01/08]
In cerebellar neurons in culture, activation of group I metabotropic glutamate receptors (mGluRs) prevents glutamate and NMDA-induced neuronal death, indicating that it interferes with the excitotoxic mechanisms leading to death. However, it is not known which step of these mechanisms is affected by mGluRs. The aims of this work were to assess: (a) whether activation of group I mGluRs (mGluR1 or mGluR5) impairs NMDA-induced activation of the glutamate-nitric oxide-cGMP pathway; (b) which mGluR (1 or 5) is responsible for this impairment and (c) whether impairment of the pathway occurs at the level of activation of soluble guanylate cyclase by nitric oxide or of activation of neuronal nitric oxide synthase (nNOS) by NMDA. It is shown that activation of mGluR1 enhances the function of the glutamate-nitric oxide-cGMP pathway by increasing activation of soluble guanylate cyclase by nitric oxide. In contrast, mGluR5 activation inhibits the glutamate-nitric oxide-cGMP pathway by reducing NMDA-induced activation of nNOS. This is due to reduced NMDA-induced increase in cAMP, reduced activation of Akt by cAMP and of nNOS by Akt. The impairment of activation of the glutamate-NO-cGMP pathway by activation of mGluR5 would contribute to its neuroprotective effect against excitotoxicity in cerebellar neurons in culture. (C) 2009 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据