Calcium efflux from cultured bovine adrenal chromaffin cells induced by pituitary adenylate cyclase-activating polypeptide (PACAP): possible involvement of an Na+/Ca2+ exchange mechanism.

The effect of pituitary adenylate cyclase-activating polypeptide 1-38 (PACAP1-38) on Ca2+ efflux from cultured bovine adrenal chromaffin cells was examined. PACAP1-38 stimulated the efflux of 45Ca2+ from the cells in a concentration dependent manner (10(-9)-10(-7)M). This effect was inhibited by its potent receptor antagonist PACAP6-38. PACAP1-38 increased the formation of [3H]inositol phosphates and cyclic AMP in the cells. Forskolin, an activator of adenylate cyclase, also stimulated the efflux of 45Ca2+ from the cells. 3-Isobutyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterase, enhanced PACAP1-38-induced 45Ca2+ efflux from the cells. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, had no effect on the efflux of 45Ca2+ from the cells. The increases in 45Ca2+ efflux induced by PACAP1-38 and forskolin were reduced by deprivation of extracellular Na+ and the Na+/Ca2+ exchange inhibitor amiloride. In addition, PACAP1-38 stimulated 22Na+ influx into the cells, and this action was inhibited by amiloride. These results suggest that PACAP1-38 stimulates an Na+/Ca2+ exchange mechanism through activation of adenylate cyclase in cultured bovine adrenal chromaffin cells.