Skip to main content
Log in

Hepatic bile formation in the rat

Addition of vasoactive intestinal peptide to the equation

  • Original Articles
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

While changes in gastric, pancreatic, and intestinal secretion in response to more recently identified gastrointestinal peptides have been characterized, there has been less investigation into effects of these hormones on hepatic bile production. The isolated perfused rat liver model has been used to examine effects of vasoactive intestinal peptide (VIP), somatostatin, bombesin, and thyrotropin-releasing hormone (TRH) on bile flow and bile acid transport. No changes were seen following bolus administration of bombesin (3×10−8–1.5×10−6 M) or TRH (3×10−7–3×10−6 M), while somatostatin (6×10−6 M) produced a small decrease in bile flow without any change in bile acid output. VIP (3×10−7 M) caused a highly significant increase in both volume of bile flow (0.85±0.8 to 1.11±0.09 μl/min/g liver,P<0.001) and bile acid output (31.6±1.5 to 43.2±1.7 nmol/min/g liver,P<0.001). Elimination of Ca2+ from liver perfusate did not prevent VIP-induced increases in bile flow and bile acid output, and no synergistic effect of concomitant theophylline administration was observed. While effects of VIP on bile flow appear to be due to alterations in hepatic transport of bile acids, the exact mechanism(s) producing these changes remains to be elucidated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Gullo L, Labo G: Thyrotropin-releasing hormone inhibits pancreatic enzyme secretion in humans. Gastroenterology 80:735–739, 1981

    Google Scholar 

  2. Pearse AGE, Polak JM, Bloom SR: The new gut hormones. Gastroenterology 72:746–761, 1977

    Google Scholar 

  3. Kaminski DL, Deshpande YG: Effect of somatostatin and bombesin on secretin-stimulated ductular bile flow in dogs. Gastroenterology 85:1239–1247, 1983

    Google Scholar 

  4. Hanks JB, Kortz WJ, Andersen DK, Scott Jones R: Somatostatin suppression of canine fasting bile secretion. Gastroenterology 84:130–137, 1983

    Google Scholar 

  5. Rene E, Danzinger RG, Hofmann AF, Nakagaki M: Pharmacologic effect of somatostatin on bile formation in the dog. Gastroenterology 84:120–129, 1983

    Google Scholar 

  6. Ricci GL, Fevery J: Cholestatic action of somatostatin in the rat: Effect on the different fractions of bile secretion. Gastroenterology 82:552–562, 1981

    Google Scholar 

  7. Makhlouf GM, Said SI, Yau WM: Interplay of vasoactive intestinal peptide (VIP) and synthetic VIP fragments with secretin and octapeptide of cholecystokinin on pancreatic and biliary secretion. Gastroenterology 66:737, 1974 (abstract)

    Google Scholar 

  8. Barnhart JL, Combes B: Erythritol and mannitol clearances with taurocholate and secretin-induced choleresis. Am J Physiol 234:E146-E156, 1978

    Google Scholar 

  9. Foker EL, Hicklin T, Sornson H: The clearance of mannitol and erythritol in rat bile. Proc Soc Exp Biol Med 126:115–119, 1967

    Google Scholar 

  10. Meyers WC, Wellman C, Quarfordt SH, Jones RS: Insulin and glucagon choleresis in the isolated perfused guinea pig liver. Proc Soc Exp Biol Med 173:56–62, 1983

    Google Scholar 

  11. Admirand WH, Small DM: The physicochemical basis of cholesterol gallstone formation in man. J Clin Invest 47: 1043–1052, 1968

    Google Scholar 

  12. Snedecor GW, Cochran WG: Statistical Methods, 6th ed. Ames, Iowa, Iowa State University Press, 1967

    Google Scholar 

  13. Balabaud C, Kron KA, Gumucio JJ: The assessment of the bile salt-nondependent fraction of canalicular bile water in the rat. J Lab Clin Med 89:393–399, 1977

    Google Scholar 

  14. Erlinger S: Hepatocyte bile secretion: Current views and controversies. Hepatology 1:352–359, 1981

    Google Scholar 

  15. Reuben A: Bile formation: Sites and mechanisms. Hepatology 4:15S-24S, 1984

    Google Scholar 

  16. Schulz I: Messenger role of calcium in function of pancreatic acinar cells. Am J Physiol 239:G335-G347 1980

    Google Scholar 

  17. Schwartz CJ, Kimberg DV, Sheerin HE, Field M, Said SI. Vasoactive intestinal peptide stimulation of adenylate cyclase and active electrolyte secretion in intestinal mucosa. J Clin Invest 54:536–544, 1974

    Google Scholar 

  18. Tompkins RK, Kraft AR, Zollinger RM: Secretin-like choleresis produced by a diarrheogenic non-beta islet cell tumor of the pancreas. Surgery 66:131–137, 1969

    Google Scholar 

  19. Rambaud J-C, Modigliani R, Matuchansky C, Bloom S, Said S, Pessayre D, Bernier J-J: Pancreatic cholera: Studies on tumoral secretions and pathophysiology of diarrhea. Gastroenterology 69:110–122, 1975

    Google Scholar 

  20. Reichen J, Berr F, Le M: Calcium deprivation increases biliary permeability and leads to failure to translocate bile acids in the perfused rat liver. Hepatology 3:834, 1983 (abstract)

    Google Scholar 

  21. Joseph SK, Coll KE, Thomas AP, Rubin R, Williamson JR: The role of extracellular Ca2+ in the response of the hepatocyte to Ca2+-dependent hormones. J Biol Chem 260: 12508–12515, 1985

    Google Scholar 

  22. Desbuquois B, Laudat MH, Laudat P: Vasoactive intestinal polypeptide and glucagon: Stimulation of adenylate cyclase activity via distinct receptors in liver and fat cell membranes. Biochem Biophys Res Commun 53:1187–1194, 1973

    Google Scholar 

  23. Anwer MS, Hegner D, Engelking LR: Essential role of sodium and chloride for theophylline-induced choleresis in the isolated perfused rat liver. Proc Soc Exp Biol Med 176:70–76, 1984

    Google Scholar 

  24. Edmondson JW, Miller BA, Lumeng L: Effect of glucagon on hepatic taurocholate uptake: Relationship to membrane potential. Am J Physiol 249:G427-G433, 1985

    Google Scholar 

  25. Thomsen OO, Larsen JA: The effect of glucagon, dibutyrylic cyclic AMP and insulin on bile production in the intact rat liver. Acta Physiol Scand 111:23–30, 1981

    Google Scholar 

  26. Sacks H, Waligora K, Matthews J, Pimstone B: Inhibition by somatostatin of glucagon-induced glucose release from the isolated perfused rat liver. Endocrinology 101:1751–1759, 1977

    Google Scholar 

  27. Grossman MI: Neural and hormonal regulation of gastrointestinal function: An overview. Annu Rev Physiol 41:27–33, 1979

    Google Scholar 

  28. Misbin RI, Wolfe MM, Morris P, Buynitzky SJ, McGuigan JE: Uptake of vasoactive intestinal peptide by rat liver. Am J Physiol 243:G103-G111, 1982

    Google Scholar 

  29. Nguyen TD, Williams JA, Gray GM: Liver vasoactive intestinal peptide (VIP) receptor is a membrane glycoprotein. Gastroenterology 88:1518, 1985 (abstract)

    Google Scholar 

  30. Berelowitz M, Kronheim S, Pimstone B, Shapiro B: Somatostatin-like immunoreactivity in rat blood: Characterization, regional differences and responses to oral and intravenous glucose. J Clin Invest 61:1410–1414, 1978

    Google Scholar 

  31. Doyle JW, Wolfe MM, McGuigan JE: Hepatic clearance of gastrin and cholecystokinin peptides. Gastroenterology 87: 60–68, 1984

    Google Scholar 

  32. Gores GJ, Miller LJ, LaRusso NF: Hepatic extraction and biliary excretion of cholecystokinin. Gastroenterology 86: 1321, 1984 (abstract)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported by National Institutes of Health grant AM-32208 and the Research Service of the Veterans Administration.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Knodell, R.G., Steele, N.M. & Stanley, L.N. Hepatic bile formation in the rat. Digest Dis Sci 32, 1290–1296 (1987). https://doi.org/10.1007/BF01296380

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01296380

Key Words

Navigation