Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Jul;86(1):323–331. doi: 10.1172/JCI114703

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

G Gomez 1, C M Townsend Jr 1, D W Green 1, S Rajaraman 1, T Uchida 1, G H Greeley Jr 1, R D Soloway 1, J C Thompson 1
PMCID: PMC296724  PMID: 1694866

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.

Full text

PDF
323

Images in this article

326Image
on p.326
327Image
on p.327
328Image
on p.328

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baxter J. N., Jenkins S. A., Day D. W., Roberts N. B., Cowell D. C., Mackie C. R., Shields R. Effects of somatostatin and a long-acting somatostatin analogue on the prevention and treatment of experimentally induced acute pancreatitis in the rat. Br J Surg. 1985 May;72(5):382–385. doi: 10.1002/bjs.1800720516. [DOI] [PubMed] [Google Scholar]
  3. Beher W. T., Beher M. E., Rao B. Bile acid and cholesterol metabolism in the mouse as affected by cholestyramine. Proc Soc Exp Biol Med. 1966 Jul;122(3):881–884. doi: 10.3181/00379727-122-31278. [DOI] [PubMed] [Google Scholar]
  4. Bondesen S., Christensen H., Lindorff-Larsen K., Schaffalitzky de Muckadell O. B. Plasma secretin in response to pure bile salts and endogenous bile in man. Dig Dis Sci. 1985 May;30(5):440–444. doi: 10.1007/BF01318176. [DOI] [PubMed] [Google Scholar]
  5. Chayvialle J. A., Miyata M., Rayford P. L., Thompson J. C. Effects of test meal, intragastric nutrients, and intraduodenal bile on plasma concentrations of immunoreactive somatostatin and vasoactive intestinal peptide in dogs. Gastroenterology. 1980 Nov;79(5 Pt 1):844–852. [PubMed] [Google Scholar]
  6. DISCHE Z. Qualitative and quantitative colorimetric determination of heptoses. J Biol Chem. 1953 Oct;204(2):983–997. [PubMed] [Google Scholar]
  7. GEHAN E. A. A GENERALIZED WILCOXON TEST FOR COMPARING ARBITRARILY SINGLY-CENSORED SAMPLES. Biometrika. 1965 Jun;52:203–223. [PubMed] [Google Scholar]
  8. Gomez G., Lluis F., Ishizuka J., Draviam E. J., Uchida T., Greeley G. H., Jr, Thompson J. C. Bile enhances release of insulin: an incretin-mediated effect. Surgery. 1987 Aug;102(2):195–199. [PubMed] [Google Scholar]
  9. Gomez G., Townsend C. M., Jr, Maani R., Singh P., Greeley G. G., Jr, Thompson J. C. Down-regulation of pancreatic growth and gallbladder contractility by bile salts. Am J Surg. 1989 Jan;157(1):20–26. doi: 10.1016/0002-9610(89)90414-5. [DOI] [PubMed] [Google Scholar]
  10. Gomez G., Upp J. R., Jr, Lluis F., Alexander R. W., Poston G. J., Greeley G. H., Jr, Thompson J. C. Regulation of the release of cholecystokinin by bile salts in dogs and humans. Gastroenterology. 1988 Apr;94(4):1036–1046. doi: 10.1016/0016-5085(88)90564-1. [DOI] [PubMed] [Google Scholar]
  11. Grundy S. M., Metzger A. L., Adler R. D. Mechanisms of lithogenic bile formation in American Indian women with cholesterol gallstones. J Clin Invest. 1972 Dec;51(12):3026–3043. doi: 10.1172/JCI107130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Grundy S. M. Treatment of hypercholesterolemia by interference with bile acid metabolism. Arch Intern Med. 1972 Oct;130(4):638–648. [PubMed] [Google Scholar]
  13. Johns W. H., Bates T. R. Quantification of the binding tendencies of cholestyramine. I. Effect of structure and added electrolytes on the binding of unconjugated and conjugated bile-salt anions. J Pharm Sci. 1969 Feb;58(2):179–183. doi: 10.1002/jps.2600580206. [DOI] [PubMed] [Google Scholar]
  14. Koop I., Fellgiebel A., Koop H., Schafmayer A., Arnold R. Effect of cholestyramine on plasma cholecystokinin and pancreatic polypeptide levels, and exocrine pancreatic secretion. Eur J Clin Invest. 1988 Oct;18(5):517–523. doi: 10.1111/j.1365-2362.1988.tb01050.x. [DOI] [PubMed] [Google Scholar]
  15. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  16. Liddle R. A., Goldfine I. D., Williams J. A. Bioassay of plasma cholecystokinin in rats: effects of food, trypsin inhibitor, and alcohol. Gastroenterology. 1984 Sep;87(3):542–549. [PubMed] [Google Scholar]
  17. Niederau C., Crass R. A., Silver G., Ferrell L. D., Grendell J. H. Therapeutic regimens in acute experimental hemorrhagic pancreatitis. Effects of hydration, oxygenation, peritoneal lavage, and a potent protease inhibitor. Gastroenterology. 1988 Dec;95(6):1648–1657. doi: 10.1016/s0016-5085(88)80091-x. [DOI] [PubMed] [Google Scholar]
  18. Niederau C., Ferrell L. D., Grendell J. H. Caerulein-induced acute necrotizing pancreatitis in mice: protective effects of proglumide, benzotript, and secretin. Gastroenterology. 1985 May;88(5 Pt 1):1192–1204. doi: 10.1016/s0016-5085(85)80079-2. [DOI] [PubMed] [Google Scholar]
  19. Niederau C., Liddle R. A., Ferrell L. D., Grendell J. H. Beneficial effects of cholecystokinin-receptor blockade and inhibition of proteolytic enzyme activity in experimental acute hemorrhagic pancreatitis in mice. Evidence for cholecystokinin as a major factor in the development of acute pancreatitis. J Clin Invest. 1986 Oct;78(4):1056–1063. doi: 10.1172/JCI112661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ohshio G., Saluja A., Leli U., Sengupta A., Steer M. L. Failure of a potent cholecystokinin antagonist to protect against diet-induced pancreatitis in mice. Pancreas. 1989;4(6):739–743. doi: 10.1097/00006676-198912000-00013. [DOI] [PubMed] [Google Scholar]
  21. Renner I. G., Wisner J. R., Jr, Rinderknecht H. Protective effects of exogenous secretin on ceruletide-induced acute pancreatitis in the rat. J Clin Invest. 1983 Sep;72(3):1081–1092. doi: 10.1172/JCI111033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Shaffer E. A., Small D. M. Biliary lipid secretion in cholesterol gallstone disease. The effect of cholecystectomy and obesity. J Clin Invest. 1977 May;59(5):828–840. doi: 10.1172/JCI108705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Stange E. F., Scheibner J., Lutz C., Ditschuneit H. Feedback regulation of bile acid synthesis in the rat by dietary vs. intravenous cholate or taurocholate. Hepatology. 1988 Jul-Aug;8(4):879–886. doi: 10.1002/hep.1840080429. [DOI] [PubMed] [Google Scholar]
  24. Turley S. D., Dietschy J. M. Re-evaluation of the 3 alpha-hydroxysteroid dehydrogenase assay for total bile acids in bile. J Lipid Res. 1978 Sep;19(7):924–928. [PubMed] [Google Scholar]
  25. Vlahcevic Z. R., Bell C. C., Jr, Buhac I., Farrar J. T., Swell L. Diminished bile acid pool size in patients with gallstones. Gastroenterology. 1970 Aug;59(2):165–173. [PubMed] [Google Scholar]
  26. Wisner J. R., Jr, Renner I. G. Asperlicin, a nonpeptidal cholecystokinin receptor antagonist, attenuates sodium taurocholate-induced acute pancreatitis in rats. Pancreas. 1988;3(2):174–179. doi: 10.1097/00006676-198804000-00011. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES