PERTUSSIS TOXIN PRETREATMENT ENHANCES CATECHOLAMINE SECRETION INDUCEDBY 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-indu ced catecholamine secretion in cultured porcine adrenal medullary cell s. Pretreatment of these cells with PTX (1 ng/ml for 24 h or 10 ng/ml for 6 h) markedly en ha need PACAP-induced catecholamine secretion. PT X pretreatment also produced a small increase in basal secretion and s ecretion 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 catecholami ne secretion by PTX and found that PACAP-induced accumulation of inosi tol phosphates in PTX-pretreated cells was significantly greater than that in untreated cells. Furthermore, removal of extracellular Ca2+ an d addition of Ca2+ channel blockers inhibited the catecholamine secret ion induced by PACAP in PTX-pretreated cells. From these results, we s peculate that a PTX-sensitive G-protein tonically inhibits phospholipa se C. PTX enhances the PACAP-induced secretion of catecholamine by blo cking the action of this inhibitory G-protein.