Antagonist-type interaction of glucocorticoids with the GABA receptor-coupled chloride channel.
The interaction of glucocorticoids, corticosterone, cortisol and cortisone, and their reduced metabolites with t-[35S]-butyl bicyclo-phosphorothionate (TBPS) binding sites was examined in vitro. At physiologically relevant concentrations glucocorticoids alter TBPS binding in a biphasic manner. At low nanomolar concentrations glucocorticoids potentiate TBPS binding (20-50% above control) and at high nanomolar and micromolar concentrations they slightly reduce it. The enhancement of TBPS binding by glucocorticoids is due to an increase in the apparent affinity and density of TBPS recognition sites and qualitatively resembles the action of bicuculline methiodide, to potentiate TBPS binding (150% above control). These findings suggest that glucocorticoids may play an important role in modulating neuronal excitability via interactions with the GABA receptor/chloride ionophore complex.
D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D001665:Binding Sites; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D002712:Chlorides; D005938:Glucocorticoids; D007473:Ion Channels; D011963:Receptors, GABA-A; D009118:Muscimol; C017069:bicuculline methiodide; C037476:tert-butylbicyclophosphorothionate; D001640:Bicuculline