Activation of NMDA receptors reverses desensitization of mGluR5 in native and recombinant systems.

Alagarsamy S, Marino MJ, Rouse ST, Gereau RW, Heinemann SF, Conn PJ
Nat Neurosci. 1999 2 (3): 234-40

PMID: 10195215 · DOI:10.1038/6338

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.

MeSH Terms (16)

Animals Hippocampus In Vitro Techniques Male Oocytes Patch-Clamp Techniques Phosphoric Monoester Hydrolases Phosphorylation Protein Kinase C Rats Rats, Sprague-Dawley Receptor, Metabotropic Glutamate 5 Receptors, Metabotropic Glutamate Receptors, N-Methyl-D-Aspartate Recombinant Proteins Xenopus

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