Entropy as the predominant driving force of binding to human recombinant αxβ3γ2 GABAA receptors

Gábor Maksay, Ruth McKernan

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In order to study the correlation of the thermodynamic driving forces of binding with the efficacies of displacing ligands, the specific binding of [3H]SR 95531 [2-(3-carboxypropyl)3-amino-6-p-methoxyphenylpyridazinium bromide], a GABAA receptor antagonist, was studied in cell lines stably expressing human α1β3γ2 and α2β3γ2 GABAA receptors. Displacing potencies for the agonists with different efficacies (muscimol, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) and piperidine-4-sulfonic acid) and for antagonists (SR 95531 and 5-(4-piperidyl)isothiazol-3-ol) were determined at 0°C, 20°C and 37°C. Displacing potencies were temperature-nearly independent for α1β3γ2 receptors. At α2β3γ2, receptor binding of the antagonists was exothermic, endothermic for the agonists THIP and piperidine-4-sulfonic acid and isothermic for muscimol. The free energy increments of displacement for the binding of the antagonist [3H]SR 95531 versus the agonist [3H]muscimol approach saturation as a function of the efficacies of the displacers only for α1β3γ2 receptors. This suggests that, for binding to α1β3γ2 GABAA receptors, displacement is an efficacy-dependent interaction predominantly driven by entropic increases.

Original languageEnglish
Pages (from-to)55-60
Number of pages6
JournalEuropean Journal of Pharmacology
Issue number1-2
Publication statusPublished - Jan 10 2001



  • Entropy change
  • GABA receptor agonist
  • GABA receptor antagonist
  • GABA receptors
  • Recombinant
  • Thermodynamics

ASJC Scopus subject areas

  • Pharmacology

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