Maiese K, Greenberg R, Boccone L, Swiriduk M
Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Neurosci Lett. 1995 Jul 21;194(3):173-6. doi: 10.1016/0304-3940(95)11753-j.
Metabotropic glutamate receptors (mGluRs) can influence neuronal survival and have been shown to be neuroprotective during glutamate toxicity in retinal cells and in cortical neurons. The mechanisms that mediate protection by this group of receptors are not clear. Since nitric oxide (NO) production can lead to neuronal cell death during excessive glutamate release, we examined whether neuronal survival was directly linked to mGluR activity and the NO pathway. Treatment with the mGluR4 receptor subtype agonist, L-(+)-2-amino-4-phosphonobutyric acid, in hippocampal cell cultures protected neurons during NO exposure. Treatment with L-(+)-2-amino-3-phosphonopropionic acid, an antagonist of the mGluR1 receptor subtype and inhibitor of inositol trisphosphate formation, did not significantly alter neuronal survival during NO administration. We conclude that activation of the mGluR4 receptor protects hippocampal neurons from NO toxicity and that the mechanism of NO induced neurodegeneration does not appear to involve inhibition of the mGluR1 receptor subtype activity or the phosphoinositide system.
代谢型谷氨酸受体（mGluRs）可影响神经元存活，且已证明在视网膜细胞和皮质神经元的谷氨酸毒性过程中具有神经保护作用。介导这组受体发挥保护作用的机制尚不清楚。由于在谷氨酸过度释放期间一氧化氮（NO）的产生可导致神经元细胞死亡，我们研究了神经元存活是否与mGluR活性及NO途径直接相关。在海马细胞培养物中用mGluR4受体亚型激动剂L-(+)-2-氨基-4-膦酰丁酸处理，可在NO暴露期间保护神经元。用mGluR1受体亚型拮抗剂和肌醇三磷酸形成抑制剂L-(+)-2-氨基-3-膦酰丙酸处理，在给予NO期间并未显著改变神经元存活情况。我们得出结论，mGluR4受体的激活可保护海马神经元免受NO毒性，且NO诱导神经退行性变的机制似乎不涉及mGluR1受体亚型活性或磷酸肌醇系统的抑制。
