Differential effects of thiocyanate on the binding thermodynamics of bicuculline methiodide versus SR95531 (gabazine) to the γ-aminobutyric acid receptor-ionophore complex

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Abstract

The temperature dependence of the binding of [3H]SR 95531 (Gabazine), an antagonist of γ-aminobutyric acid (GABA(A)) receptors, was studied in synaptosomal membranes of rat brain in the presence of 50 mM KSCN. The displacing potencies of the antagonists bicuculline methiodide and Gabazine were determined at five temperatures between 0°and 37°. Van't Hoff plots of the displacing potencies were analyzed by linear regression in the presence and absence of thiocyanate. Thiocyanate hardly affected the exothermic ionic binding interaction of gabazine. In contrast, thiocyanate strongly potentiated the binding of bicuculline methiodide and deprived it of its exothermic nature. The enhanced binding of bicuculline methiodide in the presence of chaotropic SCN- ions might be reconciled with 'entropic trapping' in a sterically constrained hydrophobic binding pocket. Copyright (C) 1998 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)729-731
Number of pages3
JournalBiochemical Pharmacology
Volume56
Issue number6
DOIs
Publication statusPublished - Sep 15 1998

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Aminobutyrates
Ionophores
Thermodynamics
Temperature
GABA-A Receptors
Linear regression
Rats
Linear Models
Brain
Ions
Membranes
gabazine
bicuculline methiodide
thiocyanate

Keywords

  • Bicuculline methiodide
  • Chaotropic effects of thiocyanate
  • GABA(A) antagonists
  • GABA(A) receptor binding
  • Gabazine (SR 95531)
  • Thermodynamics of binding

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Differential effects of thiocyanate on the binding thermodynamics of bicuculline methiodide versus SR95531 (gabazine) to the γ-aminobutyric acid receptor-ionophore complex",
abstract = "The temperature dependence of the binding of [3H]SR 95531 (Gabazine), an antagonist of γ-aminobutyric acid (GABA(A)) receptors, was studied in synaptosomal membranes of rat brain in the presence of 50 mM KSCN. The displacing potencies of the antagonists bicuculline methiodide and Gabazine were determined at five temperatures between 0°and 37°. Van't Hoff plots of the displacing potencies were analyzed by linear regression in the presence and absence of thiocyanate. Thiocyanate hardly affected the exothermic ionic binding interaction of gabazine. In contrast, thiocyanate strongly potentiated the binding of bicuculline methiodide and deprived it of its exothermic nature. The enhanced binding of bicuculline methiodide in the presence of chaotropic SCN- ions might be reconciled with 'entropic trapping' in a sterically constrained hydrophobic binding pocket. Copyright (C) 1998 Elsevier Science Inc.",
keywords = "Bicuculline methiodide, Chaotropic effects of thiocyanate, GABA(A) antagonists, GABA(A) receptor binding, Gabazine (SR 95531), Thermodynamics of binding",
author = "G. Maksay",
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T1 - Differential effects of thiocyanate on the binding thermodynamics of bicuculline methiodide versus SR95531 (gabazine) to the γ-aminobutyric acid receptor-ionophore complex

AU - Maksay, G.

PY - 1998/9/15

Y1 - 1998/9/15

N2 - The temperature dependence of the binding of [3H]SR 95531 (Gabazine), an antagonist of γ-aminobutyric acid (GABA(A)) receptors, was studied in synaptosomal membranes of rat brain in the presence of 50 mM KSCN. The displacing potencies of the antagonists bicuculline methiodide and Gabazine were determined at five temperatures between 0°and 37°. Van't Hoff plots of the displacing potencies were analyzed by linear regression in the presence and absence of thiocyanate. Thiocyanate hardly affected the exothermic ionic binding interaction of gabazine. In contrast, thiocyanate strongly potentiated the binding of bicuculline methiodide and deprived it of its exothermic nature. The enhanced binding of bicuculline methiodide in the presence of chaotropic SCN- ions might be reconciled with 'entropic trapping' in a sterically constrained hydrophobic binding pocket. Copyright (C) 1998 Elsevier Science Inc.

AB - The temperature dependence of the binding of [3H]SR 95531 (Gabazine), an antagonist of γ-aminobutyric acid (GABA(A)) receptors, was studied in synaptosomal membranes of rat brain in the presence of 50 mM KSCN. The displacing potencies of the antagonists bicuculline methiodide and Gabazine were determined at five temperatures between 0°and 37°. Van't Hoff plots of the displacing potencies were analyzed by linear regression in the presence and absence of thiocyanate. Thiocyanate hardly affected the exothermic ionic binding interaction of gabazine. In contrast, thiocyanate strongly potentiated the binding of bicuculline methiodide and deprived it of its exothermic nature. The enhanced binding of bicuculline methiodide in the presence of chaotropic SCN- ions might be reconciled with 'entropic trapping' in a sterically constrained hydrophobic binding pocket. Copyright (C) 1998 Elsevier Science Inc.

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KW - Thermodynamics of binding

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