Benzodiazepine Enhancement of γ‐Aminobutyric Acid‐Mediated Chloride Ion Flux in Rat Brain Synaptoneurosomes

Publisher Website
Google Scholar
Abstract
Benzodiazepine agonists such as Ro 11–6896 [B10(+)], diazepam, clonazepam, and flurazepam were found to enhance muscimol‐stimulated 36Cl− uptake into rat cerebral cortical synaptoneurosomes. The rank order of potentiation was B10(+) > diazepam > clonazepam > flurazepam. These bedazepines had no effect on 36Cl− uptake in the absence of muscimol. Further, the inactive en‐antiomer, Ro 11–6893 [B10(‐)], and the peripheral benzodiazepine receptor ligand Ro 5–4864 did not potentiate muscimol‐stimulated 36Cl− uptake at concentrations up to 10 μM. In contrast, the benzodiazepine receptor inverse agonists ethyl‐β‐carboline‐3‐carboxylate and 6,7‐dimethoxy‐4‐ethyl‐β‐carboline‐3‐carboxylic acid methyl ester Benzodiazepines and β‐carbolines altered the apparent K0.5 of muscimol‐stimulated 36Cl− uptake, without affecting the Vmax. The effects of both benzodiazepine receptor agonists and inverse agonists were reversed by the benzodiazepine antagonists Ro 15–1788 and CGS‐8216. These data further confirm that central benzodiazepine receptors modulate the capacity of γ‐aminobutyric acid receptor agonists to enhance chloride transport and provide a biochemical technique for studying benzodiazepine receptor function in vitro.