Gastroenterology
Volume 136, Issue 7 , Pages 2040-2044 , June 2009

New Insights Into the Mechanisms of Pancreatitis

  • Herbert Y. Gaisano

      Affiliations

    • Department of Medicine, University of Toronto, Toronto, Ontario, Canada
    • Corresponding Author InformationReprint requests Herbert Y. Gaisano, Room 7310 Medical Sciences Building, University of Toronto, Toronto, Ontario, Canada M5S1A8. fax: 416-978-8765
    • ,
  • Fred S. Gorelick

      Affiliations

    • Department of Internal Medicine, Connecticut VA Healthcare and Yale University, West Haven, Connecticut

References 

  1. Pandol SJ, Saluja AK, Imrie CW, et al. Acute pancreatitis: bench to the bedside. Gastroenterology. 2007;133:1056.e1–1056.e25
  2. Jerrells TR, Vidlak D, Strachota JM. Alcoholic pancreatitis: mechanisms of viral infections as cofactors in the development of acute and chronic pancreatitis and fibrosis. J Leukoc Biol. 2007;81:430–439
  3. Gaisano HY, Lutz MP, Leser J, et al. Supramaximal cholecystokinin displaces Munc18c from the pancreatic acinar basal surface, redirecting apical exocytosis to the basal membrane. J Clin Invest. 2001;108:1597–1611
  4. Chaudhuri A, Kolodecik TR, Gorelick FS. Effects of increased intracellular cAMP on carbachol-stimulated zymogen activation, secretion, and injury in the pancreatic acinar cell. Am J Physiol Gastrointest Liver Physiol. 2005;288:G235–G243
  5. Nemoto T, Kimura R, Ito K, et al. Sequential-replenishment mechanism of exocytosis in pancreatic acini. Nat Cell Biol. 2001;3:253–258
  6. Scheele G, Adler G, Kern H. Exocytosis occurs at the lateral plasma membrane of the pancreatic acinar cell during supramaximal secretagogue stimulation. Gastroenterology. 1987;92:345–353
  7. Otani T, Chepilko SM, Grendell JH, et al. Codistribution of TAP and the granule membrane protein GRAMP-92 in rat caerulein-induced pancreatitis. Am J Physiol. 1998;275:G999–G1009
  8. Hashimoto D, Ohmuraya M, Hirota M, et al. Involvement of autophagy in trypsinogen activation within the pancreatic acinar cells. J Cell Biol. 2008;181:1065–1072
  9. Sherwood MW, Prior IA, Voronina SG, et al. Activation of trypsinogen in large endocytic vacuoles of pancreatic acinar cells. Proc Natl Acad Sci U S A. 2007;104:5674–5679
  10. Gukovskaya AS, Vaquero E, Zaninovic V, et al. Neutrophils and NADPH oxidase mediate intrapancreatic trypsin activation in murine experimental acute pancreatitis. Gastroenterology. 2002;122:974–984
  11. Rothman JE. Lasker Basic Medical Research Award (The machinery and principles of vesicle transport in the cell). Nat Med. 2002;8:1059–1062
  12. Gaisano HY. A hypothesis: SNARE-ing the mechanisms of regulated exocytosis and pathologic membrane fusions in the pancreatic acinar cell. Pancreas. 2000;20:217–226
  13. Rizo J, Sudhof TC. Snares and Munc18 in synaptic vesicle fusion. Nat Rev Neurosci. 2002;3:641–653
  14. Lam PP, Cosen Binker LI, Lugea A, et al. Alcohol redirects CCK-mediated apical exocytosis to the acinar basolateral membrane in alcoholic pancreatitis. Traffic. 2007;8:605–617
  15. Cosen-Binker LI, Lam PP, Binker MG, et al. Alcohol-induced protein kinase C-alpha phosphorylation of Munc18c in carbachol-stimulated acini causes basolateral exocytosis. Gastroenterology. 2007;132:1527–1545
  16. Gaisano HY, Sheu L, Foskett JK, et al. Tetanus toxin light chain cleaves a vesicle-associated membrane protein (VAMP) isoform 2 in rat pancreatic zymogen granules and inhibits enzyme secretion. J Biol Chem. 1994;269:17062–17066
  17. Wang CC, Ng CP, Lu L, et al. A role of VAMP8/endobrevin in regulated exocytosis of pancreatic acinar cells. Dev Cell. 2004;7:359–371
  18. Cosen-Binker L, Binker MG, Wang CC, et al. VAMP8 is the v-SNARE mediating basolateral exocytosis in alcoholic pancreatitis. J Clin Invest. 2008;118:2535–2551
  19. Mooren FCh, Hlouschek V, Finkes T, et al. Early changes in pancreatic acinar cell calcium signaling after pancreatic duct obstruction. J Biol Chem. 2003;278:9361–9369

 Conflicts of interest The authors disclose no conflicts.

 Funding Research support from the NIH (DK54201 to FSG, AA015579 to HYG), US Army Medical Research Acquisition Activity (W81XWH-07-1-0307 to HYG) and the Veterans Administration (Merit Award to FSG).

PII: S0016-5085(09)00568-X

doi: 10.1053/j.gastro.2009.04.023

Gastroenterology
Volume 136, Issue 7 , Pages 2040-2044 , June 2009

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