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

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, 3Hpropyl-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 weight 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 macromolecule may be associated to the agonist site.