9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Vacuolar ATPase regulates zymogen activation in pancreatic acini.

      The Journal of Biological Chemistry
      Amylases, secretion, Animals, Calcium, metabolism, Carbachol, pharmacology, Cell Membrane, drug effects, Cells, Cultured, Ceruletide, Chloroquine, Chymotrypsin, Enzyme Activation, Enzyme Precursors, Hydrogen-Ion Concentration, Macrolides, Male, Monensin, Pancreas, cytology, enzymology, Protein Subunits, agonists, Protein Transport, Rats, Rats, Sprague-Dawley, Solubility, Thapsigargin, Trypsin, Vacuolar Proton-Translocating ATPases, antagonists & inhibitors

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Supramaximal concentrations of cholecystokinin or its analogue caerulein have been shown to stimulate the proteolytic activation of zymogens within the pancreatic acinar cell and initiate acute pancreatitis. Previous studies suggest that a low pH compartment might be required for activation. To test this hypothesis, the effects of agents that modulate intracellular pH on caerulein-induced trypsin and chymotrypsin activation were studied. Pretreatment of pancreatic acini with the proto-ionophore monensin (10 microM) and the weak base chloroquine (40 microM) inhibited activation. Pre-incubation with the vacuolar ATPase (V-ATPase) inhibitors bafilomycin A(1) and concanamycin A also decreased activation in a concentration-dependent manner with 50% inhibition at approximately 50 and 25 nM, respectively. Caerulein stimulation caused a time- and concentration-dependent translocation of soluble V-ATPase V(1) subunits to a membrane fraction, a marker of V-ATPase activation. Carbachol also stimulated translocation at supramaximal concentrations. Elevation of cytosolic Ca(2+) by thapsigargin was sufficient to induce translocation. Thus, stimulation of V-ATPase activity appears to be required for agonist-induced zymogen activation in the pancreatic acinar cell.

          Related collections

          Author and article information

          Comments

          Comment on this article