Activation of NMDA receptors reverses desensitization of mGluR5 in native and recombinant systems
Activation of NMDA receptors reverses desensitization of mGluR5 in native and recombinant systems
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DOI：
10.1038/6338
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发表时间：
1999-03-01
影响因子：
25
通讯作者：
Conn, PJ
中科院分区：
文献类型：
--
作者：
Alagarsamy, S;Marino, MJ;Conn, PJ
代谢型谷氨酸受体mGluR5在诱导NMDA受体依赖性形式的突触可塑性和兴奋性毒性中具有关键作用。这可能是由这两种谷氨酸受体亚型之间的相互正反馈相互作用介导的，其中mGluR5的激活增强NMDA受体电流，而NMDA受体激活增强mGluR5介导的反应。我们研究了NMDA受体激活调节mGluR 5功能的机制，并发现证据表明这种反应是由蛋白磷酸酶的激活和mGluR 5上蛋白激酶C磷酸化位点的去磷酸化介导的。这种形式的神经调节在许多涉及NMDA受体激活的正常和病理过程中可能是重要的。
The metabotropic glutamate receptor, mGluR5, has a critical role in induction of NMDA-receptor-dependent forms of synaptic plasticity and excitotoxicity. This is likely mediated by a reciprocal positive-feedback interaction between these two glutamate receptor subtypes in which activation of mGluR5 potentiates NMDA receptor currents and NMDA receptor activation potentiates mGluR5-mediated responses. We have investigated the mechanism by which NMDA receptor activation modulates mGluR5 function and find evidence that this response is mediated by activation of a protein phosphatase and a resultant dephosphorylation of protein kinase C phosphorylation sites on mGluR5. This form of neuromodulation may be important in a number of normal and pathological processes that involve activation of the NMDA receptor.