title: Ex vivo binding of t-[35S )butylbicyclophosphorothionate: a biochemical tool to study the pharmacology of ethanol at the gamma-aminobutyric acid-coupled chloride channel.
abstract: The effects of acute administration of ethanol on t-[35S]Butylbiclophosphorothionate (35S-TBPS) binding measured ex vivo in unwashed membrane preparations of rat cerebral cortex were investigated. Ethanol, given i.g., decreased in a dose-related (0.5-4 g/kg) and time-dependent manner the binding of 35S-TBPS. This effect was similar to that induced by the administration of diazepam (0.5-4 mg/kg i.p.). Scatchard plot analysis of this radioligand binding revealed that ethanol, differently from diazepam, decreased the apparent affinity of 35S-TBPS recognition sites whereas it failed to change the density of these binding sites. The effect of ethanol on 35S-TBPS binding could not be reversed by the previous administration to rats of the benzodiazepine receptor antagonist, Ro 15-1788 (ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H- imidazo[1,5a][1,4]benzodiazepine-3-carboxylate). Vice versa, the benzodiazepine receptor partial inverse agonist, Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H- imidazo[1,5a][4,4]benzodiazepine-3-carboxylate) (8 mg/kg i.p.), prevented completely ethanol-induced decrease of 35S-TBPS binding. The ability of Ro 15-4513 to prevent the action of ethanol was shared by the anxiogenic and proconvulsant beta-carboline derivatives, FG 7142 (N-methyl-beta-carboline-3-carboxamide) (12.5 mg/kg i.p.) and ethyl-beta-carboline-3-carboxylate (0.6 mg/kg i.v.), which, per se, enhanced this parameter. Moreover, ethanol (0.5-4 g/kg) was able to reverse the increase of 35S-TBPS binding elicited by the s.c. injection of isoniazid (350 mg/kg) and to clearly attenuate the severity of tonic-clonic seizures produced by this inhibitor of the GABAergic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Experimental Biology, University of Cagliari, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Sanna
authors.forename: A
authors.initials: A
authors.lastname: Concas
authors.forename: M
authors.initials: M
authors.lastname: Serra
authors.forename: G
authors.initials: G
authors.lastname: Santoro
authors.forename: G
authors.initials: G
authors.lastname: Biggio
mesh_terms: D000818:Animals; D001386:Azides / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002712:Chlorides / Q000378:metabolism*; D003292:Convulsants / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects; D007538:Isoniazid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D013462:Sulfur Radioisotopes; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D001386:Azides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002712:Chlorides; D003292:Convulsants; D007473:Ion Channels; D011963:Receptors, GABA-A; D013462:Sulfur Radioisotopes; D001569:Benzodiazepines; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; C037476:tert-butylbicyclophosphorothionate; C042957:Ro 15-4513; D003975:Diazepam; D007538:Isoniazid