Effects of chaotropic anions on bicuculline inhibition of high affinity γ-aminobutyric acid binding in bovine retina and rat brain membranes

Abstract

Chaotropic anions (ions that favour transfer of apolar groups to water) increased bicuculline inhibition of (3)H-?-aminobutyric acid binding to bovine retinal membranes as previously reported for rat forebrain membranes. The increased bicuculline inhibition was reversible when the chaotropic anion was removed thus ruling out the possibility that 'endogenous regulators' were being removed by the chaotropic anions. Another possible explanation for the enhanced bicuculline inhibition is an increase in the solubility of bicuculline, an organic compound that is sparingly soluble in water; however, when bicuculline-methiodide, a more water soluble form of bicuculline was used, no difference was noted in this enhancement. Although the chaotropic anions temporarily increase the bicuculline inhibition of ?-aminobutyric acid binding, they do not increase (3)H-?-aminobutyric acid receptor binding as previously suggested. Thiocyanate or perchlorate have no effect on (3)H-?-aminobutyric acid receptor binding to rat forebrain or cerebellar membranes. Although thiocyanate slightly inhibits ?-aminobutyric acid receptor binding to bovine retinal membranes, perchlorate has no effect. The previous observation that sodium perchlorate enhanced ?-aminobutyric acid binding in bovine retina was due to the enhancement of sodium-dependent binding to a nipecotic acid-sensitive binding site (perhaps an uptake site). The mechanism of action of chaotropic anions in vitro on ?-aminobutyric acid binding may be through an alteration in the interaction of the receptor with the antagonists, bicuculline or bicuculline-methiodide, but is not through the removal of a component that blocks the binding site or regulates the receptor's properties, as evidenced by the reversibility of the chaotropic anion effect and the lack of effect on agonist binding.