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Surgical Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
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 · h1
for intervals up to 3 h, and the changes were contrasted with those in
animals receiving saline or 0.25 µg · kg1 · h1
caerulein. Saline or 0.25 µg · kg1 · h1
caerulein did not induce significant changes. In contrast, 5 µg · kg1 · h1
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
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