Mechanism of Calcium on ATP–and Bradykinin-induced Mucin Secretion from Human Pulmonary Mucoepidermoid Carcinoma Cell Lines

Abstract

We have shown previously that extracellular ATP and bradykinin can stimulate the release of mucin from cultured human pulmonary mucoepidermoid carcinoma cells (NCI-H292) (Kusano et al 1997). Using this same cell culture system, we studied the mechanism by which this ATP- and bradykinin-induced mucin release occurs. We found that the mucin secretory response to ATP was not significantly affected by extracellular Ca2+ depletion, but the response to bradykinin was significantly inhibited by Ca2+-free medium. ATP and bradykinin increased the concentration of free intracellular Ca2+ ([Ca2+]i); the ATP-stimulated response was not affected by extracellular Ca2+ depletion, the bradykinin-stimulated response was prevented in the absence of extracellular Ca2+. ATP and bradykinin enhanced the accumulation of inositol 1,4,5-triphosphate in NCI-H292 cells and pretreatment with pertussis toxin blocked the increase in mucin secretion induced by extracellular ATP or bradykinin. These results suggest that extracellular ATP and bradykinin stimulate mucin release from NCI-H292 cells by a signal transduction that seems to involve ATP- or bradykinin-activated receptors associated with phospholipase C via pertussis toxin-sensitive GTP-binding proteins. These findings may suggest a new direction of research into the regulation of airway mucin secretion.