AJP - GI Add DOIs to your references at manuscript stage!
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol 292: G1594-G1599, 2007. First published March 1, 2007; doi:10.1152/ajpgi.00500.2006
0193-1857/07 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
292/6/G1594    most recent
00500.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Husain, S. Z.
Right arrow Articles by Shah, A. U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Husain, S. Z.
Right arrow Articles by Shah, A. U.

HORMONES AND SIGNALING

Caerulein-induced intracellular pancreatic zymogen activation is dependent on calcineurin

Sohail Z. Husain,1 Wayne M. Grant,1 Fred S. Gorelick,2 Michael H. Nathanson,2 and Ahsan U. Shah1

Departments of 1Pediatrics and 2Internal Medicine, Yale University School of Medicine and Veterans Affairs Connecticut Health Care, New Haven, Connecticut

Submitted 26 October 2006 ; accepted in final form 22 February 2007

Aberrant cytosolic Ca2+ flux in pancreatic acinar cells is critical to the pathological pancreatic zymogen activation observed in acute pancreatitis, but the downstream effectors are not known. In this study, we examined the role of Ca2+-activated protein phosphatase 2B (or calcineurin) in zymogen activation. Isolated pancreatic acinar cells were stimulated with supraphysiological caerulein (100 nM) with or without the calcineurin inhibitors FK506 or cell-permeable calcineurin inhibitory peptide (CiP). Chymotrypsin activity was measured as a marker of zymogen activation, and the percent amylase secretion was used as a measure of enzyme secretion. Cytosolic Ca2+ changes were recorded in acinar cells loaded with the intermediate Ca2+-affinity dye fluo-5F using a scanning confocal microscope. A 50% reduction in chymotrypsin activity was observed after pretreatment with 1 µM FK506 or 10 µM CiP. These pretreatments did not affect amylase secretion or the rise in cytosolic Ca2+ after caerulein stimulation. These findings suggest that calcineurin mediates caerulein-induced intra-acinar zymogen activation but not enzyme secretion or the initial caerulein-induced cytosolic Ca2+ signal.

pancreatitis; protein phosphatase 2B; pancreatic acinar; calcium signaling


Address for reprint requests and other correspondence: S. Husain, Dept. of Pediatrics, 333 Cedar St., FMP408, PO Box 208064, New Haven, CT 06520 (e-mail: sohail.husain{at}yale.edu)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.