Pertussis toxin pretreatment enhances catecholamine secretion induced by pituitary adenylate cyclase-activating polypeptide in cultured porcine adrenal medullary chromaffin cells: a possible role of the inositol lipid cascade.

We determined how pertussis toxin (PTX) pretreatment alters PACAP-induced catecholamine secretion in cultured porcine adrenal medullary cells. Pretreatment of these cells with PTX (1 ng/ml for 24 h or 10 ng/ml for 6 h) markedly enhanced PACAP-induced catecholamine secretion. PTX pretreatment also produced a small increase in basal secretion and secretion in response to nicotine and carbachol, but the effect of the PACAP-induced secretion was most striking. We examined the role of the phosphoinositol cascade in potentiating the PACAP-induced catecholamine secretion by PTX and found that PACAP-induced accumulation of inositol phosphates in PTX-pretreated cells was significantly greater than that in untreated cells. Furthermore, removal of extracellular Ca2+ and addition of Ca2+ channel blockers inhibited the catecholamine secretion induced by PACAP in PTX-pretreated cells. From these results, we speculate that a PTX-sensitive G-protein tonically inhibits phospholipase C. PTX enhances the PACAP-induced secretion of catecholamine by blocking the action of this inhibitory G-protein.