title: Progressive disruption of acinar cell calcium signaling is an early feature of cerulein-induced pancreatitis in mice.
abstract: OBJECTIVE
  Disruption of pancreatic exocrine secretion is an important feature of acute pancreatitis. Because cytosolic calcium is a key intracellular messenger controlling pancreatic secretion, this study examined patterns of calcium signaling during the early stages of cerulein-induced pancreatitis.
  
  
  METHODS
  Mice were administered hourly intraperitoneal injections of cerulein (50 micrograms/kg), and paired controls were administered saline. Acini were isolated by collagenase from pancreatic tissue harvested after injections 1, 3, 5, and 7 and were loaded with Fura-2. Individual cellular calcium responses to acetylcholine and cholecystokinin were studied using digital imaging.
  
  
  RESULTS
  The proportion of cells maintaining a normal oscillatory calcium response to physiological secretagogue stimulation diminished progressively after increasing cerulein injections. Also, the normal polarized spatial pattern of calcium Increase within individual acinar cells was progressively lost. A sustained response to high-dose stimulation was maintained but with diminishing amplitude. The characteristic calcium response to the Ca(2+)-adenosine triphosphatase inhibitor thapsigargin was maintained, implying that calcium reuptake and extrusion were not impaired.
  
  
  CONCLUSIONS
  Progressive disruption of physiological patterns of pancreatic acinar cell calcium signaling, notably in the secretory pole of the cell, is an early feature of pancreatitis induced by cerulein hyperstimulation. These changes may be important in contributing to the disruption of exocrine secretion in acute pancreatitis.
authors.affiliation: Physiological Laboratory, University of Liverpool, England.
authors.forename: J B
authors.initials: JB
authors.lastname: Ward
authors.forename: R
authors.initials: R
authors.lastname: Sutton
authors.forename: S A
authors.initials: SA
authors.lastname: Jenkins
authors.forename: O H
authors.initials: OH
authors.lastname: Petersen
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000208:Acute Disease; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002108:Ceruletide; D002766:Cholecystokinin / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism*; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
chemical_list: D004791:Enzyme Inhibitors; D013729:Terpenes; D019284:Thapsigargin; D002108:Ceruletide; D002766:Cholecystokinin; D000252:Calcium-Transporting ATPases; D000109:Acetylcholine; D002118:Calcium