Involvement of phosphoinositide metabolism in GABA-induced catecholamine release from cultured bovine adrenal chromaffin cells

Abstract

The effects of GABA on catecholamine release and phosphoinositide metabolism were studied in cultured bovine adrenal chromaffin cells. GABA and muscimol, a specific agonist for the GABA A receptor, each evoked a gradual secretion of catecholamines from the cells in the presence of ouabain, an inhibitor of Na +,K +-ATPase. This release was inhibited by bicuculline, a specific antagonist for the GABA A receptor, or by picrotoxin, a blocker of GABA-gated Cl − channels, and was potentiated by diazepam or pentobarbital. GABA or muscimol induced a concentration-dependent formation of inositol phosphates. This accumulation of inositol phosphates was also inhibited by bicuculline, picrotoxin or removal of extracellular Ca 2+, and also potentiated by diazepam and pentobarbital. Nicardipine suppressed GABA-induced catecholamine release in the presence of ouabain and accumulation of inositol phosphates, while verapamil, diltiazem, and ω-conotoxin failed to inhibit these responses to GABA. The phosphoinositide-specific phospholipase C inhibitor neomycin also inhibited both GABA-induced accumulation of inositol phosphates and stimulation of catecholamine release in the presence of ouabain. These results taken together indicate that GABA evoked catecholamine release from the chromaffin cells in the presence of ouabain by stimulation of phosphoinositide metabolism in a Ca 2+-sensitive manner via activation of GABA A receptor-coupled Cl − channels.