Synaptic non-GluN2B-containing NMDA receptors regulate tyrosine phosphorylation of GluN2B 1472 tyrosine site in rat brain slices.

Activation of N-methyl-D-aspartate receptors (NMDARs) mediates changes in the phosphorylation status of the glutamate receptors themselves. Previous studies have indicated that during synaptic activity, tyrosine kinases (Src and Fyn) or phosphatases (PTPα and STEP) are involved in regulating the phosphorylation of NMDARs. In this study, we used immunoblotting to investigate the role of an NMDAR subpopulation on the phosphorylation level of the GluN2B subunit at the Y1336 and Y1472 sites in rat brain slices after NMDA treatment. We found that NMDA stimulation dramatically decreased the phosphorylation level of GluN2B at Y1472 in a dose- and time-dependent manner, but not at Y1336. Extrasynaptic NMDAR activation did not reduce the phosphorylation of GluN2B at Y1472. In addition, ifenprodil, a selective antagonist of GluN2B-containing NMDARs, did not abolish the decreased phosphorylation of GluN2B at Y1472 triggered by NMDA. These results suggest that the activation of synaptic GluN2A-containing NMDARs is required for the decreased phosphorylation of GluN2B at Y1472 that is induced by NMDA treatment in rat brain slices.