Entropy as the predominant driving force of binding to human recombinant α β3γ2 GABAA receptors

摘要: Abstract In order to study the correlation of thermodynamic driving forces binding with efficacies displacing ligands, specific [ 3 H]SR 95531 [2-(3-carboxypropyl)3-amino-6- p -methoxyphenylpyridazinium bromide], a GABA A receptor antagonist, was studied in cell lines stably expressing human α 1 β γ 2 and receptors. Displacing potencies for agonists different (muscimol, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) piperidine-4-sulfonic acid) antagonists (SR 5-(4-piperidyl)isothiazol-3-ol) were determined at 0°C, 20°C 37°C. temperature-nearly independent At , exothermic, endothermic THIP acid isothermic muscimol. The free energy increments displacement antagonist versus agonist H]muscimol approach saturation as function displacers only This suggests that, receptors, is an efficacy-dependent interaction predominantly driven by entropic increases.