title: Bimodal action of furosemide on convulsant [3H]EBOB binding to cerebellar and cortical GABA(A) receptors.
abstract: 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.
authors.affiliation: Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest.
authors.forename: G
authors.initials: G
authors.lastname: Maksay
authors.forename: E R
authors.initials: ER
authors.lastname: Korpi
authors.forename: M
authors.initials: M
authors.lastname: Uusi-Oukari
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D003292:Convulsants / Q000378:metabolism*; D005665:Furosemide / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D007700:Kinetics; D009544:Niflumic Acid / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002712:Chlorides; D003292:Convulsants; D018757:GABA Modulators; D011963:Receptors, GABA-A; C091518:1-(4-ethynylphenyl)-4-propyl-2,6,7-trioxabicyclo(2.2.2)octane; D009544:Niflumic Acid; D005680:gamma-Aminobutyric Acid; D005665:Furosemide; D010424:Pentobarbital