Bimodal action of furosemide on convulsant [3H]EBOB binding to cerebellar and cortical GABA(A) receptors.

Picrotoxinin-sensitive binding of a convulsant 4'-ethynyl-4-n[2,3-3H2]propyl-bicycloorthobenzoate ([3H]EBOB) to gamma-aminobutyric acid type A (GABA(A)) receptors was characterized in rat cerebrocortical and cerebellar membranes. The non-penetrating organic anions, furosemide and niflumate, in spite of their structural similarities, exerted differential effects on [3H]EBOB binding. Furosemide, a loop diuretic and a specific antagonist of a cerebellar GABA(A) receptor population, and GABA decreased the inhibitory potencies of each other in the cerebellum, while enhanced them in the cortex. The inhibitory potencies of niflumate, an anti-inflammatory and a chloride channel blocker. and GABA were enhanced by each other both in the cerebellum and cortex. Removal of chloride ions did not modify the effects of furosemide on [3H]EBOB binding. Furosemide antagonized the inhibition of cerebellar [3H]EBOB binding by a low pentobarbital concentration (0.1 mM), but enhanced the inhibition by a high concentration (0.5 mM). The results indicate that [3H]EBOB binding can be used to detect the known pharmacological features of the cerebellar granule cell-specific 16 subunit-containing GABA(A) receptors. The data extends the properties of furosemide antagonism of this receptor subtype to chloride insensitivity and interactions with barbiturate sites.