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

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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 (Bmax=1.86 pmol/mg protein) with relatively low affinity (KD= 45 nM). l-Glutamate, glycine. and spermidine produced concentration-dependent increases in specific [3H]MK-801 binding due to a reduction in the Kd of the radioligand. In the presence of high concentrations of l-glutamate, glycine, or spermidine, the KD 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, KD= 6.2 nM; l-glutamate + spermidine, KD= 2.2 nM: