Autoradiographic characterization of the non‐N‐methyl‐D‐aspartate binding sites in human cerebellum using the antagonist [3H]6‐cyano‐7‐nitroquinoxaline‐2,3‐dione

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Abstract
Using quantitative autoradiography, we have characterized the binding properties of the non‐N‐methyl‐D‐aspartate (NMDA) glutamate receptor antagonist [3H]6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) in adult human cerebellum. Saturation experiments revealed [3H]CNQX binding to a single class of sites with similar affinity in the molecular and granule cell layer (Kd = 89.0 ± 6.4 and 83.3 ± 9.9nM, respectively). The maximum number of [3H]CNQX binding sites was much higher in the molecular compared to the granule cell layer (Bmax = 16.2 ± 1.1 and 2.8 ± 0.5 pmol/mg protein, respectively). Inhibition experiments were performed in order to examine the pharmacological profile of [3H]CNQX binding in the molecular layer. [3H]CNQX labeled sites with high affinity for both non‐NMDA agonists, (RS)‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) and kainate. Dose‐response curves for inhibition of [3H]CNQX by AMPA and Kainate were biphasic. The potency of AMPA for displacement of [3H]CNQX binding (Ki © 1994 Wiley‐Liss, Inc.:2.8 ± 0.8 nM and 12.5 ± 0.8 μM) was 4‐ to 6‐fold greater than the corresponding potency of kainate (Ki:18.1 ± 5.7 nm and 48.7 ± 9.3 μM). In conclusion, the pharmacological analysis of [3H]CNQX binding in the human cerebellar molecular layer reflects the existence of multiple binding sites of the non‐NMDA receptor that have different affinities for both AMPA and kainate.

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