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

Vijay P. Singh, Ashok Saluja, Lakshmi Bhagat, Antti J. Hietaranta, Albert Song, Andreas Mykoniatis, Gijs J.D. Van Acker, Michael L. Steer

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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 Nα-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.

Original languageEnglish (US)
Pages (from-to)1818-1827
Number of pages10
JournalGastroenterology
Volume120
Issue number7
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

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Serine Proteinase Inhibitors
Actins
Calcium
Ceruletide
Serine Proteases
Second Messenger Systems
Bombesin
Secretin
Acinar Cells
Vasoactive Intestinal Peptide
Carbachol
Amylases
Ketones
Phenylalanine
Actin Cytoskeleton
Adenosine
Staining and Labeling
Enzymes

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Serine protease inhibitor causes F-actin redistribution and inhibition of calcium-mediated secretion in pancreatic acini. / Singh, Vijay P.; Saluja, Ashok; Bhagat, Lakshmi; Hietaranta, Antti J.; Song, Albert; Mykoniatis, Andreas; Van Acker, Gijs J.D.; Steer, Michael L.

In: Gastroenterology, Vol. 120, No. 7, 01.01.2001, p. 1818-1827.

Research output: Contribution to journalArticle

Singh, VP, Saluja, A, Bhagat, L, Hietaranta, AJ, Song, A, Mykoniatis, A, Van Acker, GJD & Steer, ML 2001, 'Serine protease inhibitor causes F-actin redistribution and inhibition of calcium-mediated secretion in pancreatic acini', Gastroenterology, vol. 120, no. 7, pp. 1818-1827. https://doi.org/10.1053/gast.2001.24883
Singh, Vijay P. ; Saluja, Ashok ; Bhagat, Lakshmi ; Hietaranta, Antti J. ; Song, Albert ; Mykoniatis, Andreas ; Van Acker, Gijs J.D. ; Steer, Michael L. / Serine protease inhibitor causes F-actin redistribution and inhibition of calcium-mediated secretion in pancreatic acini. In: Gastroenterology. 2001 ; Vol. 120, No. 7. pp. 1818-1827.
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