AMPA reduces surface expression of NR1 through regulation of GSK3beta.

Emerging evidence has suggested that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) protects neurons from glutamate-induced neurotoxicity. In this study, we examined the effect of AMPA on the cell surface expression of the N-methyl-D-aspartate (NMDA) receptor, a central player in glutamate-induced neurotoxicity, using rat cortical neurons. AMPA (10 microM, 24 h) attenuated the expression of cell surface NR1, an NMDA receptor subunit, and also inhibited glutamate-induced increases in intracellular Ca2+. SB216763, an inhibitor of glycogen synthase kinase 3beta (GSK3beta), had effects similar to those of AMPA. We have earlier shown that AMPA treatment attenuated GSK3beta activity. Our data suggest that AMPA reduces the cell surface expression of NMDA receptors through the regulation of GSK3beta and, consequently, reduces the amount of intracellular Ca2+.