DIFFERENTIAL-EFFECTS OF THIOCYANATE ON THE BINDING THERMODYNAMICS OF BICUCULLINE METHIODIDE VERSUS SR95531 (GABAZINE) TO THE GAMMA-AMINOBUTYRIC-ACID RECEPTOR-IONOPHORE COMPLEX

The temperature dependence of the binding of [H-3]SR 95531 (Gabazine), an antagonist of gamma-aminobutyric acid (GABA(A)) receptors, was stu died in synaptosomal membranes of rat brain in the presence of 50 mM K SCN. The displacing potencies of the antagonists bicuculline methiodid e and Gabazine were determined at five temperatures between 0 degrees and 37 degrees. Van't Hoff plots of the displacing potencies were anal yzed by linear regression in the presence and absence of thiocyanate. Thiocyanate hardly affected the exothermic ionic binding interaction o f gabazine. In contrast, thiocyanate strongly potentiated the binding of bicuculline methiodide and deprived it of its exothermic nature. Th e enhanced binding of bicuculline methiodide in the presence of chaotr opic SCN- ions might be reconciled with ''entropic trapping'' in a ste rically constrained hydrophobic binding pocket. (C) 1998 Elsevier Scie nce Inc.