Molecular target size analyses of the NMDA-receptor complex in rat cortex

Abstract

The molecular weights of different subunits of the NMDA-receptor complex were determined by high-energy radiation inactivation analyses of the binding of [ 3H]L-glutamate, [ 3 H](3-(±)-2-( carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), [ 3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine (TCP) and [ 3H]glycine to rat cortical membranes. The molecular target sizes of [ 3H]L-glutamate binding (the recognition site), [ 3H]TCP binding (the ionophore) and [ 3H]glycine (a modulatory unit) were similar: 121 000, 118 000 and 115 000 Da, respectively. These results suggest that the three subunits are on the same protein. The molecular weigth of [ 3H]CPP binding was 209 000 Da. This suggests that in order to bind [ 3H]CPP (a competitive antagonist) with high affinity an additional macrmolecule may be associated to the agonist site.