Protective action of luminal bile salts in necrotizing acute pancreatitis in mice

Guillermo Gomez, Courtney M. Townsend, Daniel W. Green, Srinivasan Rajaraman, Tatsuo Uchida, George H. Greeley, Roger D. Soloway, James C. Thompson

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Bile salts in the intestinal lumen act to inhibit the release of cholecystokinin (CCK). Recent studies have shown that CCK may play a permissive role in the development of acute pancreatitis. In this study, the amount of luminal bile salts in female Swiss Webster mice was either decreased by feeding 4% (wt/ wt) cholestyramine or increased by feeding 0.5% sodium taurocholate for 1 wk. Plasma levels of CCK were stimulated by cholestyramine and inhibited by taurocholate. Then, acute pancreatitis was induced either by caerulein injections, or by feeding a choline-deficient, ethionine-supplemented (CDE) diet. Feeding of cholestyramine significantly decreased survival from 25% to 0% in the CDE pancreatitis, and increased the magnitude of elevation of serum amylase levels and the extent of pancreatic necrosis in both models of pancreatitis; CCK-receptor blockade with CR-1409 completely abolished the adverse effects of cholestyramine. In contrast, feeding of taurocholate significantly increased survival to 100% and decreased the elevation of serum amylase and pancreatic necrosis; CCK-8 antagonized these actions of taurocholate. Luminal bile salts appear to provide a physiologic protection against necrotizing pancreatitis, at least in part, both by inhibiting the release of CCK and by promoting resistance of the pancreas to CCK excessive stimulation in vivo.

Original languageEnglish (US)
Pages (from-to)323-331
Number of pages9
JournalJournal of Clinical Investigation
Volume86
Issue number1
DOIs
StatePublished - Jul 1990

Keywords

  • Acute pancreatitis
  • Bile salts
  • Cholecystokinin

ASJC Scopus subject areas

  • Medicine(all)

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    Gomez, G., Townsend, C. M., Green, D. W., Rajaraman, S., Uchida, T., Greeley, G. H., Soloway, R. D., & Thompson, J. C. (1990). Protective action of luminal bile salts in necrotizing acute pancreatitis in mice. Journal of Clinical Investigation, 86(1), 323-331. https://doi.org/10.1172/JCI114703