Article date: 1987/12/1
PubMed ID: 2830123
Journal name: European journal of pharmacology (ISSN: 0014-2999)
Cultured neurons from embryonic rat brain display central type benzodiazepine receptors characterized by high-affinity binding of [3H]flunitrazepam which is allosterically enhanced in the presence of gamma-aminobutyric acid (GABA). A 48 h treatment of the cultured neurons with 1 microM diazepam, 0.1 microM clonazepam or 0.1 microM beta-carboline ester derivatives did not change either Bmax or KD values of the [3H]flunitrazepam specific binding. A 48 h incubation in the presence of GABA (1 mM) or muscimol (0.1 mM) induced a 30% decrease of the Bmax value of [3H]flunitrazepam specific binding without change of the KD value. The down-regulation was dependent on GABA concentrations and temperature, and was partially inhibited by bicuculline but not by the benzodiazepine antagonist Ro 15-1788. The other subunits of the benzodiazepine-GABA-chloride channel receptor complex also seemed to be down-regulated by GABA since there was a decrease of the specific binding of [3H]muscimol and [35S]t-butylbicyclophosphorothionate (TBPS) to the GABAA and chloride channel sites respectively. The GABA-induced down-regulation of the GABA-benzodiazepine receptor seems to be selective since the specific binding of ligands to other receptors was not affected. Our results suggests that activation of the low-affinity GABA subunit which is involved in cellular electrophysiological responses, induced the receptor down-regulation.
Author List: Maloteaux J M, Octave J N, Gossuin A, Laterre C, Trouet A
Publication Types: Journal Article; Research Support, Non-U.S. Gov't
Substances mentioned in the article: GABA Antagonists; Receptors, GABA-A; gamma-Aminobutyric Acid; Flunitrazepam; Bicuculline;
Mesh terms: Animals; Bicuculline/pharmacology; Flunitrazepam/metabolism; GABA Antagonists; In Vitro Techniques; Neurons/metabolism; Radioligand Assay; Rats; Receptors, GABA-A/drug effects; gamma-Aminobutyric Acid/pharmacology;