Article date: 1987/2/24
PubMed ID: 3032339
Journal name: Brain research (ISSN: 0006-8993)
The interaction of the 'neurosteroid', pregnenolone-sulfate (PS), with the GABA/benzodiazepine/chloride ionophore receptor complex was investigated in rat brain subcellular preparations. At low micromolar concentrations PS competitively inhibited the binding of the convulsant [35S]t-butylbicyclophosphorothionate (TBPS) and antagonized pentobarbital-stimulated [3H]flunitrazepam binding to synaptosomes. In addition, PS inhibited muscimol-stimulated 36Cl-uptake in brain synaptoneurosomes, including that PS has characteristics of a relatively potent antagonist of the chloride channel coupled to the GABA receptor. Together with our previous finding that A-ring reduced metabolites of progesterone and deoxycorticosterone also interact with the GABA receptor complex but as hypnotic barbiturates, these data suggest that the regulation of GABAergic neurotransmission by various neurosteroids may be an important mechanism for controlling neuronal excitability.
Author List: Majewska M D, Schwartz R D
Publication Types: Journal Article
Substances mentioned in the article: Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Chlorides; Receptors, GABA-A; pregnenolone sulfate; Picrotoxin; Muscimol; tert-butylbicyclophosphorothionate; Pregnenolone;
Mesh terms: Adrenal Glands/physiology; Animals; Binding Sites; Brain/metabolism; Bridged Bicyclo Compounds/metabolism; Bridged Bicyclo Compounds, Heterocyclic; Chlorides/antagonists & inhibitors; Male; Muscimol/antagonists & inhibitors; Picrotoxin/metabolism; Pregnenolone/metabolism; Rats; Rats, Inbred Strains; Receptors, GABA-A/drug effects; Stimulation, Chemical;