Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain.
Neurosci Lett. 2011 Aug 15;500(2):144-7. doi: 10.1016/j.neulet.2011.06.024. Epub 2011 Jun 21.
At nerve terminals G protein coupled receptors modulate neurotransmitter release probability. We recently showed that prolonged activation of metabotropic glutamate receptor 7, mGlu7 receptor, potentiates glutamate release. This signalling involves phospholipase C activation via a pertussis toxin insensitive G protein, the hydrolysis of phosphatidylinositol (4,5)-bisphosphate, and the subsequent activation of the non-kinase diacylglycerol binding protein Munc13-1 which primes synaptic vesicle for exocytosis at the active zone. Here we found that inhibitors of diacylglycerol metabolism (diacylglycerol kinase inhibitor II and diacylglycerol lipase inhibitor RHC80267) remarkably reduce the time of mGlu7 receptor stimulation required for glutamate release potentiation in mice cerebrocortical nerve terminals. We conclude that changes in diacylglycerol levels at nerve terminals control the efficiency of the exocytotic release machinery.
在神经末梢，G 蛋白偶联受体调节神经递质释放概率。我们最近表明，代谢型谷氨酸受体 7（mGlu7 受体）的长期激活可增强谷氨酸释放。这种信号转导涉及通过百日咳毒素不敏感 G 蛋白激活磷脂酶 C，水解磷脂酰肌醇（4,5）-二磷酸，随后激活非激酶二酰基甘油结合蛋白 Munc13-1，该蛋白在活性区为突触囊泡的胞吐作用做好准备。在这里，我们发现二酰基甘油代谢抑制剂（二酰基甘油激酶抑制剂 II 和二酰基甘油脂肪酶抑制剂 RHC80267）可显著减少在小鼠大脑皮质神经末梢中增强谷氨酸释放所需的 mGlu7 受体刺激时间。我们得出结论，神经末梢中二酰基甘油水平的变化控制着胞吐释放机制的效率。
