Abstract
The present study was undertaken to evaluate the role of serine proteases in regulating digestive enzyme secretion in pancreatic acinar cells. Isolated acini were stimulated by various secretagogues in the presence or absence of cell-permeant serine protease inhibitors 4-(2-aminoethyl)-benzenesulfonyl fluoride and N(alpha)-p-tosyl-L-phenylalanine chloromethyl ketone. F-actin distribution was studied after staining with rhodamine phalloidin. Both cell-permeant serine protease inhibitors blocked amylase secretion in response to secretagogues that use calcium as a second messenger (e.g., cerulein, carbamylcholine, and bombesin) but not to those that use adenosine 3',5'-cyclic monophosphate (cAMP) as a second messenger (e.g., secretin and vasoactive intestinal polypeptide). Incubation of the acini with these inhibitors also resulted in a dramatic redistribution of the F-actin cytoskeleton. This redistribution was energy dependent. Similar redistribution of F-actin from the apical to the basolateral region was also observed when acini were incubated with a supramaximally stimulating concentration of cerulein, which is known to inhibit secretion. These results suggest that a serine protease activity is essential for maintaining the normal apical F-actin distribution; its inhibition redistributes F-actin from the apical to the basolateral region and blocks secretion induced by secretagogues that act via calcium. cAMP reverses the F-actin redistribution and hence cAMP-mediated secretion is not affected.
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