Calcium signaling of pancreatic acinar cells in the pathogenesis of pancreatitis

World J Gastroenterol. 2014 Nov 21;20(43):16146-52. doi: 10.3748/wjg.v20.i43.16146.

Abstract

Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy. The pathogenesis of pancreatitis is still not well understood. Calcium (Ca(2+)) is a versatile carrier of signals regulating many aspects of cellular activity and plays a central role in controlling digestive enzyme secretion in pancreatic acinar cells. Ca(2+) overload is a key early event and is crucial in the pathogenesis of many diseases. In pancreatic acinar cells, pathological Ca(2+) signaling (stimulated by bile, alcohol metabolites and other causes) is a key contributor to the initiation of cell injury due to prolonged and global Ca(2+) elevation that results in trypsin activation, vacuolization and necrosis, all of which are crucial in the development of pancreatitis. Increased release of Ca(2+) from stores in the intracellular endoplasmic reticulum and/or increased Ca(2+) entry through the plasma membrane are causes of such cell damage. Failed mitochondrial adenosine triphosphate (ATP) production reduces re-uptake and extrusion of Ca(2+) by the sarco/endoplasmic reticulum Ca(2+)-activated ATPase and plasma membrane Ca(2+)-ATPase pumps, which contribute to Ca(2+) overload. Current findings have provided further insight into the roles and mechanisms of abnormal pancreatic acinar Ca(2+) signals in pancreatitis. The lack of available specific treatments is therefore an objective of ongoing research. Research is currently underway to establish the mechanisms and interactions of Ca(2+) signals in the pathogenesis of pancreatitis.

Keywords: Calcium signaling; Cell injury; Overload; Pancreatic acinar cells; Pancreatitis.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channel Blockers / therapeutic use
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Calcium Signaling* / drug effects
  • Drug Design
  • Endoplasmic Reticulum / metabolism
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Mitochondria / metabolism
  • Molecular Targeted Therapy
  • Pancreas, Exocrine / drug effects
  • Pancreas, Exocrine / metabolism*
  • Pancreas, Exocrine / pathology
  • Pancreatitis / diagnosis
  • Pancreatitis / drug therapy
  • Pancreatitis / metabolism*
  • Sarcoplasmic Reticulum / metabolism
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / antagonists & inhibitors
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Enzyme Inhibitors
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium