Benzodiazepines facilitate the stimulatory action of gamma-aminobutyric acid (GABA) on basal and veratridine-evoked catecholamine release from cultured bovine adrenal chromaffin cells.

Effects of benzodiazepines were investigated on the gamma-aminobutyric acid-induced modulation of the basal and veratridine-evoked catecholamine release from cultured bovine adrenal chromaffin cells. GABA by itself, caused catecholamine release and facilitated veratridine-evoked catecholamine release. Midazolam enhanced the GABA-evoked catecholamine release in a dose-related fashion and further facilitated the enhancement by GABA of the veratridine-evoked catecholamine release. Clonazepam, a selective central-type benzodiazepine receptor agonist, also enhanced the GABA-induced catecholamine release, whereas ethyl-beta-carboline-3-carboxylate, an inverse agonist of the benzodiazepine receptor, reduced the GABA-evoked catecholamine release. The dose-response curve of the GABA-evoked catecholamine release was shifted to the left by midazolam without affecting the maximal response to GABA. Facilitation by midazolam and clonazepam of the GABA action or inhibition by ethyl-beta-carboline-3-carboxylate was antagonized by RO15-1788, which by itself had no effect on the basal or GABA- and veratridine-evoked catecholamine release. These results suggest that the central-type benzodiazepine receptor participates in the GABAergic modulation of the catecholamine release from adrenal chromaffin cells.