Activation of NMDA receptors reverses desensitization of mGluR5 in native and recombinant systems.
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.
Alagarsamy
S
S
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Marino
M J
MJ
Rouse
S T
ST
Gereau
R W
RW
Heinemann
S F
SF
Conn
P J
PJ
D000818:Animals; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009865:Oocytes; D018408:Patch-Clamp Techniques; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D011994:Recombinant Proteins; D014981:Xenopus
C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D011493:Protein Kinase C; D010744:Phosphoric Monoester Hydrolases