• CGP 39653;
  • glutamate;
  • glycine;
  • MK801;
  • NMDA receptor;
  • PSD-95


Coexpression of PSD-95c-Myc with NR1-1a/NR2A NMDA receptors in human embryonic kidney (HEK) 293 cells resulted in a decrease in efficacy for the glycine stimulation of [3H]MK801 binding similar to that previously described for l-glutamate. The inhibition constants (KIs) for the binding of l-glutamate and glycine to NR1-1a/NR2A determined by [3H]CGP 39653 and [3H]MDL 105 519 displacement assays, respectively, were not significantly different between NR1-1a/NR2A receptors coexpressed ± PSD-95c-Myc. The increased EC50 for l-glutamate enhancement of [3H]MK801 binding was also found for NR1-2a/NR2A and NR1-4b/NRA receptors thus the altered EC50 is not dependent on the N1, C1 or C2 exon of the NR1 subunit. The NR1-4b but not the NR1-1a subunit was expressed efficiently at the cell surface in the absence of NR2 subunits. Total NR1-4b and NR1-4b/NR2A expression was enhanced by PSD-95c-Myc but whole cell enzyme-linked immunoadsorbent assays (ELISAs) showed that this increase was not due to increased expression at the cell surface. It is suggested that PSD-95c-Myc has a dual effect on NMDA receptors expressed in mammalian cells, a reduction in channel gating and an enhanced expression of NMDA receptor subunits containing C-terminal E(T/S)XV PSD-95 binding motifs.