Elsevier

Brain Research

Volume 414, Issue 2, 30 June 1987, Pages 357-364
Brain Research

GABAA receptor blockers reverse the inhibitory effect of GABA on brain-specific [35S]TBPS binding

https://doi.org/10.1016/0006-8993(87)90017-5Get rights and content

Abstract

Thirteen sustances previously reported to antagonize the electrophysiological effects of γ-aminobutyric acid (GABA) on neurons also reversed the inhibitory effects of GABA on specific [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding to sites on rat brain membranes in vitro with a rank-order of potentcies similar to those found in electrophysiological (R 5135 > pitrazepin > bicuculline> SR 95103 > securinine) confirming the earlier conclusion that GABA inhibits [35S]TBPS binding by acting allosterically on relevant GABAA receptors. Pitrazepin is the most potent of a series of mono N-aryl piperazines that block GABAA receptors. The new aryl amino pyridazine GABA derivative SR 95531 was about 3-fold more potent than bicuculline and 39-fold more potent than the structurally related SR 95103. Four known GABA antagonists have the same rank orders of potencies as convulsants and as reversers of GABA's inhibitory action on [35S]TBPS binding (bicuculline > securinine > theophylline > caffeine). Reversal of GABA-induced suppression of [35S]TBPS binding provides a simple method for further characterizing GABAA receptors linked to TBPS binding sites, and facilitates identification of convulsants and novel, perhaps selective, GABA antagonists.

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