Acute oxidative stress modulates secretion and repetitive Ca2+ spiking in rat exocrine pancreas

Biochim Biophys Acta. 1999 May 31;1454(1):19-30. doi: 10.1016/s0925-4439(99)00021-6.


The effects of the oxidant tert-butylhydroperoxide (t-buOOH) on carbachol-stimulated pancreatic secretion in the vascularly perfused rat pancreas have been studied in parallel with [Ca2+]i signalling and amylase output in perifused rat pancreatic acinar cells. Perfusion of the pancreas with t-buOOH (0.1-1 mM) caused a rapid and irreversible inhibition of carbachol-stimulated (3x10-7 M) amylase and fluid secretion. Pre-perfusion of the pancreas with vitamin C and dithiothreitol or a cocktail of GSH and GSH-precursor amino acids provided only marginal protection against the deleterious effects of t-buOOH, even though GSH levels were elevated significantly. In perifused pancreatic acini, repetitive [Ca2+]i spikes evoked by carbachol (3x10-7 M) were sustained for 40 min. t-buOOH (1 mM) acutely increased the amplitude and duration of Ca2+ spikes, then attenuated Ca2+ spiking and subsequently caused a marked and sustained rise in [Ca2+]i. t-buOOH-induced alterations in carbachol-stimulated [Ca2+]i signalling and amylase release in perifused pancreatic acini were prevented by vitamin C. Although vitamin C restored impaired Ca2+ signalling and maintained amylase output in pancreatic acini, it seems likely that oxidative stress inhibits fluid secretion irreversibly in the intact pancreas, resulting in a loss of amylase output. Thus, perturbations in [Ca2+]i signalling may not fully explain the secretory block caused by oxidative stress in acute pancreatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amylases / metabolism
  • Animals
  • Antioxidants / pharmacology
  • Ascorbic Acid / pharmacology
  • Calcium / metabolism*
  • Carbachol / antagonists & inhibitors
  • Glutathione / pharmacology
  • Male
  • Maleates / pharmacology
  • Oxidative Stress*
  • Pancreas / drug effects
  • Pancreas / metabolism*
  • Perfusion
  • Rats
  • Rats, Sprague-Dawley
  • tert-Butylhydroperoxide / pharmacology


  • Antioxidants
  • Maleates
  • Carbachol
  • tert-Butylhydroperoxide
  • Amylases
  • diethyl maleate
  • Glutathione
  • Ascorbic Acid
  • Calcium