Non-NMDA glutamate receptor antagonist 3H-CNOX binds with equal affinity to two agonist states of quisqualate receptors.

Binding of 3H-CNQX to rat cortical membranes is saturable and reversible. Apparently, 3H-CNQX binds to a single site with KD = 39 nM. However, studies using AMPA as inhibitor revealed a biphasic inhibition of 3H-CNQX binding. The results suggest that CNQX binds with the same affinity to two different sites. The molecular target size of 3H-CNQX binding (51.8 +/- 3.4 kD) is equivalent to the size of the high affinity 3H-AMPA binding sites, but different from the high affinity 3H-kainate binding sites. A monoexponential decay curve for the high energy radiation inactivation analysis of 3H-CNQX binding indicates that the two 3H-CNQX binding sites have the same molecular weight and therefore might be two different conformations of the same receptor. The standard excitatory amino acids quisqualate, AMPA and kainate have a different rank order of potency as binding inhibitors at the two conformations of the quisqualate receptor.