Signal transduction pathways mediating mucin secretion from intestinal goblet cells

Cholinergic stimulation of the HT29-18N2 goblet cell line increased mucin secretion as assessed: (1) with a mucin-specific immunoassay, (2) using whole-mount immunocytochemistry, or (3) by morphometric quantification of intracellular mucous granule stores. Cholinergic stimulation did not, however, result in the apical plasmalemmal membrane cavitation that is characteristic of recent compound exocytotic activity. The resposse was not dependent on protein kinase C activation since it was not inhibited by the kinase C antagonist H7 or potentiated by the diaacylglycerol kinase antagonist R59022. Calcium ionophore A23187 also accelerated mucin secretion by a noncompound exocytotic pathway. Activation of protein kinase C by phorbol 12-myristate 13-acetate, on the other hand, increased mucin secretion by a compound exocytotic pathway. The results provide insight into the signal transduction pathways underlying secretory responses of goblet cells observedin situ.This research was supported by funding from the National Institutes of Health (DK38587), the Cystic Fibrosis Foundation, and the Crohn's and Colitis Foundation of America. The image analysis system was purchased with the assistance of the University of Missouri Institutional Biomedical Research Support Grant RR07053 from the National Institutes of Health.