Ca2+ signalling and pancreatitis: effects of alcohol, bile and coffee

Trends Pharmacol Sci. 2006 Feb;27(2):113-20. doi: 10.1016/ Epub 2006 Jan 6.


Ca2+ is a universal intracellular messenger that controls a wide range of cellular processes. In pancreatic acinar cells, acetylcholine and cholecystokinin regulate secretion via generation of repetitive local cytosolic Ca2+ signals in the apical pole. Bile acids and non-oxidative alcohol metabolites can elicit abnormal cytosolic Ca2+ signals that are global and sustained and result in necrosis. Necrosis results from excessive loss of Ca2+ from the endoplasmic reticulum, which is mediated by Ca2+ release through specific channels and inhibition of Ca2+ pumps in intracellular stores, followed by entry of extracellular Ca2+. Reduction of the cellular ATP level has a major role in this process. These abnormal Ca2+ signals, which can be inhibited by caffeine, explain how excessive alcohol intake and biliary disease cause acute pancreatitis, an often-fatal human disease in which the pancreas digests itself and its surroundings.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bile / physiology*
  • Calcium Signaling / drug effects*
  • Central Nervous System Depressants / pharmacology*
  • Coffee*
  • Ethanol / pharmacology*
  • Humans
  • Pancreatitis / drug therapy
  • Pancreatitis / pathology
  • Pancreatitis / physiopathology*
  • Protein Kinase C / physiology


  • Central Nervous System Depressants
  • Coffee
  • Ethanol
  • Protein Kinase C