Calcium efflux from cultured bovine adrenal chromaffin cells induced by pituitary adenylate cyclase-activating polypeptide (PACAP): Possible involvement of an Na+/Ca2+ 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 45 Ca 2+ from the cells in a concentration dependent manner (10 −9 –10 −7 M). This effect was inhibited by its potent receptor antagonist PACAP 6–38 . PACAP 1–38 increased the formation of [ 3 H]inositol phosphates and cyclic AMP in the cells. Forskolin, an activator of adenylate cyclase, also stimulated the efflux of 45 Ca 2+ from the cells. 3-Isobutyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterase, enhanced PACAP 1–38 -induced 45 Ca 2+ efflux from the cells. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, had no effect on the efflux of 45 Ca 2+ from the cells. The increases in 45 Ca 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 22 Na + 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.