NMDA receptor activation by spermine requires glutamate but not glycine.

Stimulation by spermine of [3H]MK-801 binding to N-methyl-D-aspartate (NMDA) receptors was additive with the effect of glutamate and glycine, but was completely abolished by the glutamate antagonist 3-(carboxypiperazin-4-yl)propyl-1-phosphonate (CPP, 10 microM) or the glycine antagonist 7-chlorokynurenate (10 microM). Blockade by 7-chlorokynurenate could be overcome in the presence of glutamate, whereas blockade by CPP was unaffected by glycine. Therefore, NMDA receptors can be activated by glutamate and spermine but not by glycine and spermine.