title: The role of calcium in pancreatitis.
abstract: OBJECTIVE
  A large, sustained increase in acinar [Ca2+]i may play a key role in the pathogenesis of acute pancreatitis. Many mechanisms which lead to cell damage in vitro and pancreatitis in vivo, such as free radicals or supraphysiological cerulein concentrations, cause a rapid increase in [Ca2+]i in pancreatic acinar cells. Little is known about why [Ca2+]i increases in some instances stimulate secretion and in other instances initiate cell death. So far, [Ca2+]i increases were thought to represent physiological signals when they occurred as oscillations at the single cell level.
  
  
  METHODS
  This paper reviews recent literature and our own original research about the role of calcium in the function of pancreatic acinar cells and the development of pancreatitis.
  
  
  RESULTS
  Recent studies showed that exposure of acinar cells to free radicals not only caused a bulk increase in [Ca2+]i but also resulted in calcium oscillations which had a lower frequency than, but similar amplitude to oscillations occurring after physiological stimuli. The absolute increase in [Ca2+]i did not definitely determine the cellular response. Instead, the duration of [Ca2+]i increase may have been more important. In contrast to previous belief of a direct relationship between [Ca2+]i oscillations and exocytosis, recent results show that radicals can induce [Ca2+]i oscillations which do not exert exocytosis but inhibit the secretory response to physiological stimuli. Further experiments showed that the [Ca2+]i release caused by radicals originates from thapsigargin-insensitive, ryanodine-sensitive stores.
  
  
  CONCLUSIONS
  The origin and duration of [Ca2+]i increases rather than their extent or oscillatory nature, determine whether the cell will secrete or die. An abnormal [Ca2+]i increase can trigger trypsin activation, acinar cell damage and acute pancreatitis. This hypothesis is supported by studies which show that calcium chelators inhibit radical-induced trypsin activation as well as cell necrosis and apoptosis. Thus, an inhibition of pathological [Ca2+]i release may have a therapeutic potential.
authors.affiliation: Department of Internal Medicine, St. Josef Hospital Oberhausen, Germany. claus.niederau@uni-duesseldorf.de
authors.forename: C
authors.initials: C
authors.lastname: Niederau
authors.forename: R
authors.initials: R
authors.lastname: Luthen
authors.forename: H
authors.initials: H
authors.lastname: Klonowski-Stumpe
authors.forename: R
authors.initials: R
authors.lastname: Schreiber
authors.forename: I
authors.initials: I
authors.lastname: Soika
authors.forename: N
authors.initials: N
authors.lastname: Sata
authors.forename: H
authors.initials: H
authors.lastname: Bing
authors.forename: D
authors.initials: D
authors.lastname: Haussinger
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001329:Autolysis / Q000503:physiopathology; D002118:Calcium / Q000502:physiology*; D002108:Ceruletide / Q000502:physiology; D002766:Cholecystokinin / Q000502:physiology; D010450:Endopeptidases / Q000502:physiology; D005089:Exocytosis / Q000502:physiology; D006801:Humans; D010195:Pancreatitis / Q000503:physiopathology*
chemical_list: D002108:Ceruletide; D002766:Cholecystokinin; D010450:Endopeptidases; D002118:Calcium