Diazepam biphasically modulates [3h]TBOB binding to the convulsant site of the GABAa receptor complex

Clementina M. van Rijn, Ris Dirksen, Elly Willems Van Bree, Gábor Maksay

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Interactions of GABA, bicuculline methochloride and diazepam with [3H]TBOB binding to rat brain membranes were evaluated in vitro. GABA displaced [3H]TBOB binding with and IC50 of 4μM and a slope factor near unity. The competitive GABA antagonist bicuculline methochloride shifted the displacement curve of GABA parallelly to the right, indicating that the interaction of GABA with [3H]TBOB binding is of an allosteric nature. In the presence of GABA, diazepam displaced the binding of [3H]TBOB according to a two-site model: a high affinity site with an IC50 of about 50 nM and a lower affinity site with an IC50 of about 30 μM. Bicuculline methochloride abolished the nanomolar displacement by diazepam and increased the micromolar IC50 value. These results indicate that the interaction of the high affinity diazepam site with the [3H]TBOB binding site is totally GABA dependent and that the low affinity effect of diazepam on [3H]TBOB binding is at least partially GABA dependent. It is likely that the low affinity potency of diazepam to displace [3H]TBOB binding has physiological relevance.

Original languageEnglish
Pages (from-to)787-800
Number of pages14
JournalJournal of Receptors and Signal Transduction
Volume15
Issue number6
DOIs
Publication statusPublished - Jan 1 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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