Neuroprotection by group I metabotropic glutamate receptor antagonists in forebrain ischemia of gerbil
Neuroprotection by group I metabotropic glutamate receptor antagonists in forebrain ischemia of gerbil
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DOI：
10.1016/s0304-3940(00)01483-x
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发表时间：
2000-10-20
影响因子：
2.5
通讯作者：
Dempsey, RJ
中科院分区：
文献类型：
--
作者：
Rao, AM;Hatcher, JF;Dempsey, RJ
I组代谢型谷氨酸受体（mGluR 1和5）的刺激激活G蛋白偶联磷脂酶C（PLC）以释放1，2-二酰基甘油（DAG）和花生四烯酸（ArAc）。为了阐明I组mGluR的作用，我们测试了（S）-α-甲基-4-羧基-苯基甘氨酸（MCPG，mGluR 1和5拮抗剂）、1-氨基茚满-1，5-二羧酸（AIDA，mGluR 1a特异性拮抗剂）和2-甲基-6-（苯乙炔基）吡啶（MPEP，mGluR 5拮抗剂）对沙土鼠短暂前脑缺血后ArAc释放和神经元存活的影响。缺血导致（a）在再灌注1天时显著的ArAc释放和（B）在海马CA中显著的神经元死亡，g天再灌注后的子区域。MCPG和MPEP减少ArAc的释放，也显着增加神经元的存活。AIDA在减少ArAc释放方面效果较差，对神经元死亡没有影响。提示mGluR 5的激活可能是短暂缺血后ArAc释放和神经元死亡的重要途径。(C)2000爱思唯尔科学爱尔兰有限公司版权所有。
Stimulation of group I metabotropic glutamate receptors (mGluR 1 and 5) activates G-protein coupled-phospholipase C (PLC) to release 1,2-diacylglycerol (DAG) and arachidonic acid (ArAc). To elucidate the role of group I mGluR, we tested the effects of (S)-alpha-methyl-4-carboxy-phenylglycine (MCPG, mGluR 1 and 5 antagonist), 1-aminoindan-1,5-dicarboxylic acid (AIDA, mGluR la specific antagonist) and 2-methyl-6-(phenylethynyl) pyridine (MPEP, mGluR 5 antagonist) on ArAc release and neuronal survival after transient forebrain ischemia in gerbils. Ischemia resulted in (a) significant release of ArAc at 1-day reperfusion and (b) significant neuronal death in the hippocampal CA, subfield after g-day reperfusion. MCPG and MPEP decreased ArAc release and also significantly increased neuronal survival. AIDA was less effective in decreasing ArAc release and had no effect on neuronal death. These results suggest that activation of mGluR 5 may be an important pathway in ArAc release and neuronal death after transient ischemia. (C) 2000 Elsevier Science ireland Ltd. All rights reserved.