Calcium efflux from cultured bovine adrenal chromaffin cells induced by pituitary adenylate cyclase-activating polypeptide (PACAP): Possible involvement of an Na+/Ca 2+ exchange mechanism

Abstract

The effect of pituitary adenylate cyclase-activating polypeptide 1–38 (PACAP 1–38) on Ca 2+ efflux from cultured bovine adrenal chromaffin cells was examined. PACAP 1–38 stimulated the efflux of 45Ca 2+ from the cells in a concentration dependent manner (10 −9–10 −7M). This effect was inhibited by its potent receptor antagonist PACAP 6–38. PACAP 1–38 increased the formation of [ 3H]inositol phosphates and cyclic AMP in the cells. Forskolin, an activator of adenylate cyclase, also stimulated the efflux of 45Ca 2+ from the cells. 3-Isobutyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterase, enhanced PACAP 1–38-induced 45Ca 2+ efflux from the cells. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, had no effect on the efflux of 45Ca 2+ from the cells. The increases in 45Ca 2+ efflux induced by PACAP 1–38 and forskolin were reduced by deprivation of extracellular Na + and the Na +/Ca 2+ exchange inhibitor amiloride. In addition, PACAP 1–38 stimulated 22Na + influx into the cells and this action was inhibited by amiloride. These results suggest that PACAP 1–38 stimulates an Na +/Ca 2+ exchange mechanism through activation of adenylate cyclase in cultured bovine adrenal chromaffin cells.