Cooperative Modulation of [3H]MK‐801 Binding to the N‐Methyl‐d‐Aspartate Receptor‐Ion Channel Complex by l‐Glutamate, Glycine, and Polyamines

Abstract

In extensively washed rat cortical membranes [³ H](+)- 5 - methyl - 10,11 - dihydro - 5 H- dibenzo [a,d]cyclohepten-5,10-imine ([³H]MK-801) labeled a homogeneous set of sites (B_max=1.86 pmol/mg protein) with relatively low affinity (K_D= 45 nM). l-Glutamate, glycine. and spermidine produced concentration-dependent increases in specific [³H]MK-801 binding due to a reduction in the K_d of the radioligand. In the presence of high concentrations of l-glutamate, glycine, or spermidine, the K_D values for [³H]MK-801 were reduced to 11 nM, 18 nM, and 15 nM, respectively. Maximally effective concentrations of combinations of the three compounds further increased [³H]MK-801 binding affinity as follows: l-glutamate + glycine, K_D= 6.2 nM; l-glutamate + spermidine, K_D= 2.2 nM: