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Subcellular kinetics of early trypsinogen activation in acute rodent pancreatitis

Subcellular kinetics of early trypsinogen activation in acute rodent pancreatitis Abstract To investigate the debated role of intracellular trypsinogen activation and its relation to lysosomal enzyme redistribution in the pathogenesis of acute pancreatitis, rats were infused with the cholecystokinin analog caerulein at 5 μg ⋅ kg −1 ⋅ h −1 for intervals up to 3 h, and the changes were contrasted with those in animals receiving saline or 0.25 μg ⋅ kg −1 ⋅ h −1 caerulein. Saline or 0.25 μg ⋅ kg −1 ⋅ h −1 caerulein did not induce significant changes. In contrast, 5 μg ⋅ kg −1 ⋅ h −1 caerulein caused significant hyperamylasemia and pancreatic edema within 30 min. Pancreatic content of trypsinogen activation peptide (TAP) increased continuously (significant within 15 min). TAP generation was predominantly located in the zymogen fraction during the first hour but expanded to other intracellular compartments thereafter. Cathepsin B activity in the zymogen compartment increased continuously throughout the experiments and correlated significantly with TAP generation in the same compartment. Total trypsinogen content increased to 143% with marked interstitial trypsinogen accumulation after 3 h. Supramaximal caerulein stimulation causes trypsinogen activation by 15 min that originates in the zymogen compartment and is associated with increasing cathepsin B activity in this subcellular compartment. However, a much larger pool of trypsinogen survives and accumulates in the extracellular space and may become critical in the evolution of necrotizing pancreatitis. pancreas protease activation acinar cell experimental cathepsin B Footnotes Address for reprint requests: A. L. Warshaw, Dept. of Surgery, Massachusetts General Hospital, 15 Parkman St., WAC 336, Boston, MA 02114. K. Mithöfer was supported by Deutsche Forschungsgemeinschaft Grant Mi 450/1–2. Copyright © 1998 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Gastrointestinal and Liver Physiology The American Physiological Society

Subcellular kinetics of early trypsinogen activation in acute rodent pancreatitis

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0193-1857
eISSN
1522-1547
Publisher site
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Abstract

Abstract To investigate the debated role of intracellular trypsinogen activation and its relation to lysosomal enzyme redistribution in the pathogenesis of acute pancreatitis, rats were infused with the cholecystokinin analog caerulein at 5 μg ⋅ kg −1 ⋅ h −1 for intervals up to 3 h, and the changes were contrasted with those in animals receiving saline or 0.25 μg ⋅ kg −1 ⋅ h −1 caerulein. Saline or 0.25 μg ⋅ kg −1 ⋅ h −1 caerulein did not induce significant changes. In contrast, 5 μg ⋅ kg −1 ⋅ h −1 caerulein caused significant hyperamylasemia and pancreatic edema within 30 min. Pancreatic content of trypsinogen activation peptide (TAP) increased continuously (significant within 15 min). TAP generation was predominantly located in the zymogen fraction during the first hour but expanded to other intracellular compartments thereafter. Cathepsin B activity in the zymogen compartment increased continuously throughout the experiments and correlated significantly with TAP generation in the same compartment. Total trypsinogen content increased to 143% with marked interstitial trypsinogen accumulation after 3 h. Supramaximal caerulein stimulation causes trypsinogen activation by 15 min that originates in the zymogen compartment and is associated with increasing cathepsin B activity in this subcellular compartment. However, a much larger pool of trypsinogen survives and accumulates in the extracellular space and may become critical in the evolution of necrotizing pancreatitis. pancreas protease activation acinar cell experimental cathepsin B Footnotes Address for reprint requests: A. L. Warshaw, Dept. of Surgery, Massachusetts General Hospital, 15 Parkman St., WAC 336, Boston, MA 02114. K. Mithöfer was supported by Deutsche Forschungsgemeinschaft Grant Mi 450/1–2. Copyright © 1998 the American Physiological Society

Journal

AJP - Gastrointestinal and Liver PhysiologyThe American Physiological Society

Published: Jan 1, 1998

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