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Elevated calcium and activation of trypsinogen in rat pancreatic acini
  1. T W Frickb,
  2. C Fernández-del-Castilloa,
  3. D Bimmlerb,
  4. A L Warshawa
  1. aDepartment of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA, bDepartment of Surgery, University Hospital of Zürich, Switzerland
  1. Mr T Frick, Level 9, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK.


Background—Acute pancreatitis associated with hypercalcaemia has been described in humans and experimental animals. It has been demonstrated that calcium dose dependently accelerates trypsinogen activation, and it is generally believed that ectopic activation of digestive enzymes is an early event in the pathophysiology of acute pancreatitis.

Aims and methods—Trypsinogen activation peptide (TAP) was measured in isolated rat pancreatic acini exposed to elevated extracellular calcium in order to investigate the association between calcium and trypsinogen activation in living cells. TAP was determined in the culture medium either before (extracellular compartment) or after (intracellular compartment) cell homogenisation.

Results—Neither secretory stimulation nor elevated calcium alone caused an increase in TAP levels. Maximal cerulein or carbachol stimulation superimposed on high medium calcium, however, significantly increased intracellular trypsinogen activation twofold. This increase was inhibited by eitherN G-monomethyl-l-arginine (l-NMMA) or verapamil. Acinar cell morphology and function remained intact as demonstrated by electron microscopy and secretagogue dose-response studies.

Conclusions—These results support the hypothesis that increased intracellular trypsinogen activation is an early step in the pathogenesis of hypercalcaemia induced pancreatitis. The model may have a bearing on other types of pancreatitis as elevated cytosolic calcium is thought to be an early event in the pathogenesis of acute pancreatitis in general.

  • hypercalcaemia
  • pancreatitis pathogenesis
  • serine proteases
  • acute pancreatitis
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