INVOLVEMENT OF A SIGNAL TRANSDUCTION MECHANISM IN ATP-INDUCED MUCIN RELEASE FROM CULTURED AIRWAY GOBLET CELLS

Release of mucins from cultured airway surface epithelial cells can be stimulated by extracellular ATP via a P2-purinergic receptor-mediated mechanism (K. C. Kim and B. C. Lee. 1991. Br. J. Pharmacol. 103:1053- 1056). In this report, we studied the mechanism by which extracellular ATP induces the mucin release. We found that: (1) ATP increased both mucin release and generation of inositol phosphates in a dose-dependen t fashion, and their dose-effect relationships were almost superimpose d; (2) the increases in both mucin release and the phosphatidylinosito l phosphate (PI) turnover by extracellular ATP were partially, but alm ost equally, blocked by the pretreatment with pertussis toxin (42% for mucin release and 44 % for PI turnover). We conclude that in cultured airway goblet cells extracellular ATP stimulates mucin release by a s ignal transduction mechanism, which seems to involve coupling of ATP-a ctivated P2 purinoceptors with phospholipase C, at least in part, via pertussis toxin-sensitive GTP-binding proteins. This may be an importa nt finding in understanding the regulation of mucin release by airway goblet cells, since a number of agents present in the airway could inf luence this signal transduction pathway and subsequently modulate the mucin secretion.