Binding of the AMPA receptor antagonist [3H]GYKI 53405 to Xenopus brain membranes.
GYKI 52466 and related 2,3-benzodiazepines are highly selective antagonists of AMPA-evoked responses in rat CNS. However, these compounds do not compete with [3H]AMPA binding and their site of action remains unclear. Here we show that [3H]GYKI 53405 binds specifically to Xenopus brain membranes with KD and Bmax values of 4.5 microM and 35 pmol mg-1 protein respectively. Binding is increased in the presence of Mg2+ and is unaffected by AMPA or kainate. This is the first report of the binding of a GYKI 52466-related radioligand to any tissue and these results provide an initial step towards the characterization of novel recognition sites which are of considerable therapeutic potential.
Szabó
G
G
Department of Pharmacology, Medical School, University of Birmingham, Edgbaston, UK.
Henley
J M
JM
D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism; D007700:Kinetics; D011869:Radioligand Assay; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D014316:Tritium; D014981:Xenopus; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D018091:Receptors, AMPA; D014316:Tritium; D001569:Benzodiazepines; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C085266:talampanel