Stimulation of benzodiazepine receptor binding by gamma-aminobutyric acid.

Abstract

The effect of the neurotransmitter GABA on high-affinity binding of benzodiazepines to brain membranes was investigated. GABA stimulated [3H]diazepam binding by more than 100% when extensively washed membranes from rat brain tissue were used. This GABA-stimulated benzodiazepine binding occurred in all brain regions examined. The stimulation was specific for GABA agonists. It was inhibited by the GABA receptor blocker bicuculline methiodide. A large number of compounds structurally closely related to GABA but without direct effect on the GABA receptor failed to enhance [3H]diazepam binding. The stimulation of benzodiazepine binding was caused by an increase in affinity; the number of binding sites remained unchanged. Half-maximal activation of [3H]diazepam binding occurred in the presence of 300 nM muscimol or 900 nM GABA. .beta.-Guanidinopropionic acid and imidazoleacetic acid were much weaker activators. The described stimulation of benzodiazepine high-affinity binding may be mediated by a receptor for GABA. This site of GABA action exhibits different properties when compared to GABA receptors, as characterized by high affinity binding of GABA agonists.