CYCLOTHIAZIDE DECREASES [H-3] AMPA BINDING TO RAT-BRAIN MEMBRANES - EVIDENCE THAT AMPA RECEPTOR DESENSITIZATION INCREASES AGONIST AFFINITY

The effects of cyclothiazide, a drug which blocks AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor desensitization, were tested on binding of [H-3]AMPA to rat brain membranes. Cyclothiazide reduced [H-3]AMPA binding by lowering the apparent affinity of the AMPA receptor. The magnitude of the decrease was temperature dependent and greater for membrane-bound than for solubilized receptors. These data provide evidence that desensitization increases the affinity of the AMPA receptor for agonists and indicate that a significant percentage of AMPA receptors in conventional equilibrium binding assays are in a desensitized state.