title: The role of Ca2+ in the pathophysiology of pancreatitis.
abstract: Acute pancreatitis is a human disease in which the pancreatic pro-enzymes, packaged into the zymogen granules of acinar cells, become activated and cause autodigestion. The main causes of pancreatitis are alcohol abuse and biliary disease. A considerable body of evidence indicates that the primary event initiating the disease process is the excessive release of Ca(2+) from intracellular stores, followed by excessive entry of Ca(2+) from the interstitial fluid. However, Ca(2+) release and subsequent entry are also precisely the processes that control the physiological secretion of digestive enzymes in response to stimulation via the vagal nerve or the hormone cholecystokinin. The spatial and temporal Ca(2+) signal patterns in physiology and pathology, as well as the contributions from different organelles in the different situations, are therefore critical issues. There has recently been significant progress in our understanding of both physiological stimulus-secretion coupling and the pathophysiology of acute pancreatitis. Very recently, a promising potential therapeutic development has occurred with the demonstration that the blockade of Ca(2+) release-activated Ca(2+) currents in pancreatic acinar cells offers remarkable protection against Ca(2+) overload, intracellular protease activation and necrosis evoked by a combination of alcohol and fatty acids, which is a major trigger of acute pancreatitis.
authors.affiliation: MRC Group, School of Biosciences, Cardiff University, The Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AX, UK. PetersenOH@cardiff.ac.uk.
authors.forename: Julia V
authors.initials: JV
authors.lastname: Gerasimenko
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Gerasimenko
authors.forename: Ole H
authors.initials: OH
authors.lastname: Petersen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D006801:Humans; D010195:Pancreatitis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D022142:Secretory Vesicles / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002118:Calcium
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