Pharmacological study on Ba2+-stimulated catecholamine secretion from cultured bovine adrenal chromaffin cells: Possible relation of Ba2+ action to Ca2+-activated secretory mechanism.

Abstract

The stimulatory action of Ba2+ on catecholamine secretion from cultured bovine adrenal chromaffin cells was studied to elucidate a possible relationship between Ba2+ action and the Ca2(+)-mediated secretory mechanism. Catecholamine secretion was dramatically stimulated by Ba2+ in the absence of external Ca2+, and this stimulatory action was observed in a concentration-dependent manner. Ba2+ evoked the concomitant release of dopamine beta-hydroxylase in a similar manner to the Ca2(+)-dependent secretion. The stimulation of catecholamine secretion by low concentrations of Ba2+ was markedly inhibited by protein kinase inhibitors, polymyxin B and trifluoperazine (TFP). The inhibitory action of polymyxin B, but not that of TFP, on the Ba2+ action was attenuated by elevating the concentration of Ba2+ in the incubation mixture. The stimulatory action of Ba2+ was enhanced by a protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA). In contrast to the acute effect of TPA, chronic exposure of chromaffin cells to high concentration of TPA reduced catecholamine secretion stimulated by Ba2+ as well as high K+ and carbamylcholine. These findings suggest the possibility that Ba2+ may activate Ca2(+)-mediated secretory processes presumably through its action on protein kinase C, thus resulting in the stimulation of catecholamine secretion from bovine adrenal chromaffin cells.