Isoniazid, an inhibitor of GABAergic transmission, enhances [35S]TBPS binding in rat cerebral cortex.
Isoniazid, administered to rats one hour before killing produced a dose-dependent enhancement of [35S]t-butylbiciclophosphorothionate ([35S]TBPS, 2 nM) measured ex vivo in unwashed membrane preparation of the cerebral cortex. Saturation experiments revealed that the effect of isoniazid was due to an increase (+36%) in the total number of [35S]TBPS binding sites. Diazepam (3 mg/kg i.p.) administered 15 min after isoniazid antagonized the enhancement of [35S]TBPS binding elicited by isoniazid. Moreover, diazepam itself induced a significant decrease (-30%) in the total number of [35S]TBPS binding sites. These results provide the first direct evidence that 'in vivo' alterations in the function of the GABA-dependent chloride channel can be detected in vitro by studying the binding of [35S]TBPS to its recognition sites in the GABAA receptor complex. Our finding suggests a new model suitable to study biochemically the function of GABAergic synapses under various physiological and pharmacological conditions.
Serra
M
M
Department of Experimental Biology, University of Cagliari, Italy.
Sanna
E
E
Biggio
G
G
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003292:Convulsants / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D007538:Isoniazid / Q000494:pharmacology*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013462:Sulfur Radioisotopes; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D003292:Convulsants; D013462:Sulfur Radioisotopes; D005680:gamma-Aminobutyric Acid; C037476:tert-butylbicyclophosphorothionate; D003975:Diazepam; D007538:Isoniazid