Protons released during pancreatic acinar cell secretion acidify the lumen and contribute to pancreatitis in mice

Behrendorff, Natasha, Floetenmeyer, Matthias, Schwiening, Christof and Thorn, Peter (2010) Protons released during pancreatic acinar cell secretion acidify the lumen and contribute to pancreatitis in mice. Gastroenterology, 139 5: 1711-1720. doi:10.1053/j.gastro.2010.07.051

Author Behrendorff, Natasha
Floetenmeyer, Matthias
Schwiening, Christof
Thorn, Peter
Title Protons released during pancreatic acinar cell secretion acidify the lumen and contribute to pancreatitis in mice
Journal name Gastroenterology   Check publisher's open access policy
ISSN 0016-5085
Publication date 2010-11
Sub-type Article (original research)
DOI 10.1053/j.gastro.2010.07.051
Volume 139
Issue 5
Start page 1711
End page 1720
Total pages 10
Editor Anil A. Rustgi
Place of publication Maryland Heights, United States
Publisher W.B. Saunders Co.
Collection year 2011
Language eng
Subject 920106 Endocrine Organs and Diseases (excl. Diabetes)
060110 Receptors and Membrane Biology
Formatted abstract
Secretory granules are acidic; cell secretion will therefore lead to extracellular acidification. We propose that during secretion, protons co-released with proteins from secretory granules of pancreatic acinar cells acidify the restricted extracellular
space of the pancreatic lumen to regulate normal physiological and pathophysiological functions in this organ

Extracellular changes in pH were quantified in real time using 2-photon microscopy
analysis of pancreatic tissue fragments from mouse models of acute pancreatitis (mice given physiological concentrations [10 -20 pM] of cholecystokinin or high
concentrations of [100 nM] cerulein). The effects of extracellular changes in pH on cell behavior and structures were measured.

With physiological stimulation, secretory granule fusion (exocytosis) caused acidification of the pancreatic lumen. Acidifications specifically affected intracellular calcium responses and accelerated the rate of recovery from agonist- evoked calcium signals. Protons therefore appear to function as negative-feedback, extracellular messengers
during coupling of cell stimuli with secretion. At high concentrations of cerulein, large increases in secretory activity were associated with extreme, prolonged acidification of the luminal space. These pathological changes in pH led to disruption of intercellular junctional coupling, measured by movement of occludin and E-cadherin.

By measuring changes in extracellular pH in pancreas of mice, we observed that luminal acidification resulted from exocytosis of zymogen granules from acinar cells. This process is part of normal organ function but could contribute to the tissue damage in cases of acute pancreatitis.
© 2010 by the AGA Institute

Keyword Epithelial
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Original title 'Protons, co-released during secretion, are a negative feedback extracellular messenger and contribute to the early tissue damage in secretagogue-induced pancreatitis'

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Biomedical Sciences Publications
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Created: Thu, 02 Sep 2010, 14:37:46 EST by Bacsweet Kaur on behalf of School of Biomedical Sciences