Serine protease inhibitor causes F-actin redistribution and inhibition of calcium-mediated secretion in pancreatic acini

Gastroenterology. 2001 Jun;120(7):1818-27. doi: 10.1053/gast.2001.24883.


Background & aims: The present study was undertaken to evaluate the role of serine proteases in regulating digestive enzyme secretion in pancreatic acinar cells.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism*
  • Adenosine Triphosphate / physiology
  • Animals
  • Bucladesine / pharmacology
  • Calcineurin / metabolism
  • Calcium / physiology*
  • Calpain / metabolism
  • Ceruletide / pharmacology
  • Cyclic AMP / physiology
  • Male
  • Pancreas / drug effects*
  • Pancreas / enzymology
  • Pancreas / ultrastructure
  • Protein Kinase C / metabolism
  • Rats
  • Rats, Wistar
  • Serine Proteinase Inhibitors / pharmacology*
  • Sulfones / pharmacology*


  • Actins
  • Serine Proteinase Inhibitors
  • Sulfones
  • 4-(2-aminoethyl)benzenesulfonylfluoride
  • Bucladesine
  • Ceruletide
  • Adenosine Triphosphate
  • Cyclic AMP
  • Protein Kinase C
  • Calcineurin
  • Calpain
  • Calcium