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.
Isobe
K
K
Department of Clinical Pathology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Nomura
F
F
Takekoshi
K
K
Nakai
T
T
D037361:Adenylate Cyclase Toxin; D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D002838:Chromaffin System / Q000378:metabolism*; D004357:Drug Synergism; D004533:Egtazic Acid / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D037342:Pertussis Toxin; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D013552:Swine; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D002121:Calcium Channel Blockers; D002395:Catecholamines; D007295:Inositol Phosphates; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010566:Virulence Factors, Bordetella; D004533:Egtazic Acid; D037342:Pertussis Toxin; D002118:Calcium