PHARMACOLOGICAL STUDY ON BA2+-STIMULATED CATECHOLAMINE SECRETION FROM CULTURED BOVINE ADRENAL CHROMAFFIN CELLS - POSSIBLE RELATION OF BA2+ ACTION TO CA2+-ACTIVATED SECRETORY MECHANISM

The stimulatory action of Ba2+ on catecholamine secretion from cultured bovine adrenal chromaffin cells was studied to elucidate a possible relationship between Ba+ 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+ may active Ca2+-mediated secretory processes presumably through its action on protein kinase C, thus resulting in the stimulation processes presumably through its action on protein kinase C, thus resulting in the stimulation of catecholamine secretion from bovine adrenal chromaffin cells.