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.
Kitayama
S
S
Department of Pharmacology, Hiroshima University School of Dentistry, Japan.
Morita
K
K
Dohi
T
T
Tsujimoto
A
A
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001479:Basal Ganglia / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D005442:Flumazenil / Q000494:pharmacology; D008874:Midazolam / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology*; D014702:Veratrine / Q000031:analogs & derivatives*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D002395:Catecholamines; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D014701:Veratridine; D014702:Veratrine; D008874:Midazolam