Document Detail

Secretin differentially sensitizes rat pancreatic acini to the effects of supramaximal stimulation with caerulein.
MedLine Citation:
PMID:  15920015     Owner:  NLM     Status:  MEDLINE    
Supramaximal stimulation of the rat pancreas with CCK, or its analog caerulein, triggers acute pancreatitis and a number of pancreatitis-associated acinar cell changes including intracellular activation of digestive enzyme zymogens and acinar cell injury. It is generally believed that some of these various acinar cell responses to supramaximal secretagogue stimulation are interrelated and interdependent. In a recent report, Lu et al. showed that secretin, by causing generation of cAMP and activation of PKA, sensitizes acinar cells to secretagogue-induced zymogen activation, and, as a result, submaximally stimulating concentrations of caerulein can, in the presence of secretin, trigger intracellular zymogen activation. We found that secretin also sensitizes acinar cells to secretagogue-induced cell injury and to subapical F-actin redistribution but that it did not alter the caerulein concentration dependence of other pancreatitis-associated changes such as the induction of a peak plateau intracellular [Ca(2+)] rise, inhibition of secretion, activation of ERK1/2, and activation of NF-kappaB. The finding that secretin sensitizes acinar cells to both intracellular zymogen activation and cell injury is consistent with the concept that these two early events in pancreatitis are closely interrelated and, possibly, interdependent. On the other hand, the finding that, in the presence of secretin, caerulein can trigger subapical F-actin redistribution without inhibiting secretion challenges the concept that disruption of the subapical F-actin web is causally related to high-dose secretagogue-induced inhibition of secretion in pancreatic acinar cells.
G Perides; A Sharma; A Gopal; X Tao; K Dwyer; B Ligon; M L Steer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2005-05-26
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  289     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-09-14     Completed Date:  2005-10-27     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G713-21     Citation Subset:  IM    
Dept. of Surgery, Tufts-New England Medical Center, Boston, MA 02111, USA.
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MeSH Terms
Actins / metabolism
Amylases / antagonists & inhibitors,  metabolism
Caerulein / pharmacology*
Cell Death / drug effects
Cyclic AMP / physiology
Cyclic AMP Response Element-Binding Protein / metabolism
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
Enzyme Precursors / pharmacology
Isoquinolines / pharmacology
MAP Kinase Kinase 2 / physiology
Mitogen-Activated Protein Kinase 1 / physiology
NF-kappa B / physiology
Pancreas / drug effects*
Rats, Sprague-Dawley
Secretin / pharmacology*
Stimulation, Chemical
Sulfonamides / pharmacology
Grant Support
P30-DK-34928-20/DK/NIDDK NIH HHS; R01-AM31396-20/AM/NIADDK NIH HHS
Reg. No./Substance:
0/Actins; 0/Cyclic AMP Response Element-Binding Protein; 0/Enzyme Precursors; 0/Isoquinolines; 0/NF-kappa B; 0/Sulfonamides; 127243-85-0/H 89; 1393-25-5/Secretin; 17650-98-5/Caerulein; 60-92-4/Cyclic AMP; EC AMP-Dependent Protein Kinases; EC Protein Kinase 1; EC Kinase Kinase 2; EC 3.2.1.-/Amylases

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