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 [3H]SR 95531 (Gabazine), an antagonist of gamma-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 degrees and 37 degrees. 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.
Maksay
G
G
Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest.
D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004396:Coloring Agents / Q000494:pharmacology*; D018756:GABA Antagonists / Q000378:metabolism* / Q000494:pharmacology; D007476:Ionophores / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D011724:Pyridazines / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism*; D013696:Temperature; D013816:Thermodynamics; D013861:Thiocyanates / Q000494:pharmacology*
D004396:Coloring Agents; D018756:GABA Antagonists; D007476:Ionophores; D011724:Pyridazines; D018079:Receptors, GABA; D013861:Thiocyanates; C017069:bicuculline methiodide; C049853:gabazine; C009941:potassium thiocyanate; D001640:Bicuculline