Cyclothiazide decreases [3H]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 [3H]AMPA to rat brain membranes. Cyclothiazide reduced [3H]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.
Hall
R A
RA
Center for the Neurobiology of Learning and Memory, University of California, Irvine 92717.
Kessler
M
M
Quan
A
A
Ambros-Ingerson
J
J
Lynch
G
G
D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004232:Diuretics; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D018091:Receptors, AMPA / Q000187:drug effects* / Q000378:metabolism; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology*; D012995:Solubility; D013696:Temperature; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism*
D001581:Benzothiadiazines; D004232:Diuretics; D018091:Receptors, AMPA; D049993:Sodium Chloride Symporter Inhibitors; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C004639:cyclothiazide