XXXX antagonists differentiate between recombinant GABAA/benzodiazepine receptor subtypes.

@entity1 @entity10483 @entity1246 @entity1027 @entity35 @entity8772 @entity21277
Seventeen @entity35 GABAA receptor subtypes were transiently expressed in the @entity1 embryonic kidney 293 cell line from alpha 1, alpha 2, alpha 3, alpha 5, or alpha 6 variants with any of the three beta subunits and gamma 2S or gamma 3. We obtained fingerprints in the form of subtype characteristic concentration-response curves of 35S-TBPS binding to @entity1246 and the GABAA antagonists @entity8772 and @entity1027 . alpha 3 beta 3 gamma 2S/3 and alpha 5 beta 3 gamma 2S/3 containing receptors effectively recognized 35S-TBPS but not when beta 3 was replaced by the @entity21277 subunit. This indicates a specific interaction of alpha and beta variants to form high-affinity 35S-TBPS binding sites. At low levels @entity1246 allosterically increased 35S-TBPS binding to all receptors with the concentration and magnitude depending on the subunit combination. Exchange of the beta variant did not alter the concentration-response curves for alpha 1 and alpha 6 containing receptors but did so for alpha 2 containing receptors. alpha 2 beta 3 gamma 3 receptors displayed strong @entity1246 -induced stimulation of 35S-TBPS binding, whereas binding to alpha 2 beta 3 gamma 3 receptors was marginally increased. @entity8772 and @entity1027 decreased 35S-TBPS binding to all gamma 3 containing receptors. In addition, @entity1027 was effective on alpha 1 beta x gamma 2 receptors. @entity8772 was threefold more potent than @entity1027 in reversing @entity1246 -induced modulation of 35S-TBPS binding in most receptor types, but was 30-fold more potent on alpha 2 @entity10483 gamma 3 and alpha 6 @entity10483 gamma 2S receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
