Is an elevated concentration of acinar cytosolic free ionised calcium the trigger for acute pancreatitis?

Lancet. 1995 Oct 14;346(8981):1016-9. doi: 10.1016/s0140-6736(95)91695-4.


The pathogenesis of acute pancreatitis is poorly understood, despite well-recognised precipitating factors. Current evidence suggests that the earliest abnormalities of acute pancreatitis arise within acinar cells, but the key intracellular trigger has yet to be identified. Within the pancreas, physiological concentrations of secretagogues bind to G-protein-linked cell-surface receptors on acinar cells, evoking short, oscillatory spikes of acinar cytosolic-free ionised calcium ([Ca2+]i), an ubiquitous intracellular messenger. Specific effects within acinar cells include initiation of enzyme release through the phosphorylation cascades of stimulus-secretion coupling. Low resting levels of [Ca2+]i are restored by Ca(2+)-ATPase, which pumps calcium into the endoplasmic reticulum and out of the cell. If high concentrations of [Ca2+]i persist, toxicity results, intracellular signalling is disrupted, and cell damage occurs. Sustained elevations in acinar [Ca2+]i result from exposure to high concentrations of secretagogues, high doses of which also induce acute pancreatitis. Similarly, sustained elevations of [Ca2+]i may result from ductal hypertension, alcohol, hypoxia, hypercalcaemia, hyperlipidaemia, viral infection, and various drugs--all factors known to precipitate acute pancreatitis. We suggest that these factors precipitate acute pancreatitis by causing either excessive release of acinar [Ca2+]i, or damage to the integrity of mechanisms that restore low resting levels of [Ca2+]i, and that the consequent calcium toxicity is the key trigger in the pathogenesis of acute pancreatitis.

Publication types

  • Review

MeSH terms

  • Acute Disease
  • Calcium / metabolism*
  • Cytosol / metabolism*
  • Homeostasis
  • Humans
  • Pancreas / cytology
  • Pancreas / metabolism
  • Pancreatitis / etiology*
  • Pancreatitis / metabolism


  • Calcium