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GABA induces down-regulation of the benzodiazepine-GABA receptor complex in the rat cultured neurons

1987; Elsevier BV; Volume: 144; Issue: 2 Linguagem: Inglês

10.1016/0014-2999(87)90517-6

1879-0712

Jean‐Marie Maloteaux, Jean‐Noël Octave, Annie Gossuin, Christian Laterre, André Trouet,

Tea Polyphenols and Effects

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 γ-aminobutyric acid (GABA). A 48 h treatment of the cultured neurons with 1 μM diazepam, 0.1 μM clonazepam or 0.1 μM β-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 choride 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.