Intra-acinar cell activation of trypsinogen during caerulein-induced pancreatitis in rats

B. Hofbauer, A. K. Saluja, M. M. Lerch, L. Bhagat, M. Bhatia, Hong Sik Lee, J. L. Frossard, G. Adler, M. L. Steer

Research output: Contribution to journalArticle

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Abstract

Supramaximal stimulation of the pancreas with the CCK analog caerulein causes acute edematous pancreatitis. In this model, active trypsin can be detected in the pancreas shortly after the start of supramaximal stimulation. Incubation of pancreatic acini in vitro with a supramaximally stimulating caerulein concentration also results in rapid activation of trypsinogen. In the current study, we have used the techniques of subcellular fractionation and both light and electron microscopy immunolocalization to identify the site of trypsinogen activation and the subsequent fate of trypsin during caerulein-induced pancreatitis. We report that trypsin activity and trypsinogen-activation peptide (TAP), which is released on activation of trypsinogen, are first detectable in a heavy subcellular fraction. This fraction is enriched in digestive enzyme zymogens and lysosomal hydrolases. Subsequent to trypsinogen activation, both trypsin activity and TAP move to a soluble compartment. Immunolocalization studies indicate that trypsinogen activation occurs in cytoplasmic vacuoles that contain the lysosomal hydrolase cathepsin B. These observations suggest that, during the early stages of pancreatitis, trypsinogen is activated in subcellular organelles containing colocalized digestive enzyme zymogens and lysosomal hydrolases and that, subsequent to its activation, trypsin is released into the cytosol.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume275
Issue number2 38-2
Publication statusPublished - 1998 Aug 1
Externally publishedYes

Fingerprint

Trypsinogen
Ceruletide
Acinar Cells
Pancreatitis
Trypsin
trypsinogen activation peptide
Hydrolases
Enzyme Precursors
Pancreas
Cathepsin B
Subcellular Fractions
Enzymes
Vacuoles
Organelles
Cytosol
Electron Microscopy
Light

Keywords

  • Cathepsin B
  • Immunolocalization
  • Pancreas
  • Subcellular fractionation
  • Trypsin
  • Trypsinogen activation peptide

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Intra-acinar cell activation of trypsinogen during caerulein-induced pancreatitis in rats. / Hofbauer, B.; Saluja, A. K.; Lerch, M. M.; Bhagat, L.; Bhatia, M.; Lee, Hong Sik; Frossard, J. L.; Adler, G.; Steer, M. L.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 275, No. 2 38-2, 01.08.1998.

Research output: Contribution to journalArticle

Hofbauer, B, Saluja, AK, Lerch, MM, Bhagat, L, Bhatia, M, Lee, HS, Frossard, JL, Adler, G & Steer, ML 1998, 'Intra-acinar cell activation of trypsinogen during caerulein-induced pancreatitis in rats', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 275, no. 2 38-2.
Hofbauer, B. ; Saluja, A. K. ; Lerch, M. M. ; Bhagat, L. ; Bhatia, M. ; Lee, Hong Sik ; Frossard, J. L. ; Adler, G. ; Steer, M. L. / Intra-acinar cell activation of trypsinogen during caerulein-induced pancreatitis in rats. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 1998 ; Vol. 275, No. 2 38-2.
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