Sorting of a constitutive secretory protein to the regulated secretory pathway of exocrine cells

Exocrine cells secrete granule proteins by regulated or constitutive-like s ecretory pathways, It is thought that all secretory proteins can enter imma ture secretory granules in exocrine cells. To test this hypothesis, we expr essed the constitutive secretory protein secreted alkaline phosphatase (SEA P) in the exocrine cell line AR42J and compared its secretion to that of am ylase, an endogenous regulated secretory protein. Secretion of SEAP and amy lase were stimulated about 1.5-fold by substance P and 2-fold by barium chl oride. In dexamethasone-treated cells, SEAP and amylase secretion were stim ulated about 1.8-fold by substance P, 5-fold by barium chloride, and 4-fold by cholecystokinin-8. Cycloheximide reduced basal secretion of SEAP and am ylase by 50%, increasing cholecystokinin-stimulated secretion to about 10-f old. Sodium butyrate induced expression of SEAP 2-fold but had no effect on stimulated secretion. These results suggest that SEAP is stored in secreto ry granules in AR42J cells. (C) 1999 Academic Press.