Iversen L, Mulvihill E, Haldeman B, Diemer N H, Kaiser F, Sheardown M, Kristensen P
Department of Pathology and Histochemistry, Novo Nordisk A/S, Måløv, Denmark.
J Neurochem. 1994 Aug;63(2):625-33. doi: 10.1046/j.1471-4159.1994.63020625.x.
Metabotropic glutamate receptors mediate their intracellular response by coupling to G proteins and may be divided into three subfamilies: mGluR1 and mGluR5, which stimulate phosphatidylinositol hydrolysis; mGluR2 and mGluR3, which are negatively coupled to cyclic AMP formation; and mGluR4 and mGluR6, which also inhibit forskolin-stimulated cyclic AMP formation. The mGluR4 subtypes may represent L-2-amino-4-phosphonobutyrate-sensitive presynaptic autoreceptors, and two alternatively spliced variants of the mGluR4 coding for two receptors with different C termini have been identified. Using in situ hybridization, we measured the levels of mGluR1-mGluR5 mRNA in regions of the rat brain 24 h after transient global ischemia, a time point when no neuronal damage can yet be observed morphologically. In the hippocampus, the mRNA levels for mGluR1, mGluR2, and mGluR5 were decreased, mGluR3 mRNA levels were unchanged, and the mGluR4 mRNA levels were strongly increased. The strongest increase appeared to be in the mRNA encoding mGluR4b. The mGluR4 mRNA was also increased in the parietal cortex, whereas the ventral posteromedial thalamic nucleus showed a small decrease in its mRNA content. These results suggest that vulnerable neurons react to an increased extracellular glutamate concentration by differential regulation of the mRNA for pre- and postsynaptically located metabotropic glutamate receptors.
代谢型谷氨酸受体通过与G蛋白偶联介导细胞内反应，可分为三个亚家族：刺激磷脂酰肌醇水解的mGluR1和mGluR5；负向偶联环磷酸腺苷形成的mGluR2和mGluR3；以及同样抑制福斯高林刺激的环磷酸腺苷形成的mGluR4和mGluR6。mGluR4亚型可能代表L-2-氨基-4-膦酰丁酸敏感的突触前自身受体，并且已鉴定出mGluR4编码具有不同C末端的两种受体的两种选择性剪接变体。我们使用原位杂交技术，在短暂性全脑缺血24小时后测量大鼠脑区mGluR1 - mGluR5 mRNA的水平，这是一个在形态学上尚未观察到神经元损伤的时间点。在海马体中，mGluR1、mGluR2和mGluR5的mRNA水平降低，mGluR3 mRNA水平未变，而mGluR4 mRNA水平显著升高。最强的升高似乎出现在编码mGluR4b的mRNA中。顶叶皮层中mGluR4 mRNA也升高，而腹后内侧丘脑核的mRNA含量略有下降。这些结果表明，易损神经元通过对突触前和突触后代谢型谷氨酸受体mRNA的差异调节，对细胞外谷氨酸浓度升高做出反应。
