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Current concepts of biliary secretion

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Abstract

Biliary secretion is reviewed. Bile acids pass along the biliary tract and small intestine without undergoing passive absorption because of their hydrophilicity and size. Active ileal absorption leads to the development of a large circulating pool of molecules and thus dissociates biliary secretion from bile acid biosynthesis (which is synonymous with cholesterol degradation). Man differs from most vertebrates in having little bile acid-independent flow; bile acid-dependent flow is also less in man than many other vertebrates. The hypercholeretic effects of certain bile acids are reviewed; the most likely explanation is cholehepatic shunting of the unconjugated, lipophilic species. Biliary lipid secretion involves bile acid-stimulated microtubule-dependent movement of phospholipid-cholesterol-rich vesicles from the Golgi to the canaliculus. Bile acid biotransformation during hepatic transport involves reconjugation (with glycine or taurine) of C24 bile acids (deconjugated during enterohepatic cycling), conjugation with glucuronate of lipophilic C23-nor bile acids, reduction of oxo groups, and epimerization of iso-(3β-hydroxy) bile acids. Glucose and amino acids enter bile from plasma as secondary solutes and are absorbed efficiently in the biliary ductular system. The biliary system is almost freely permeable to plasma Ca2+; in bile, Ca2+ is bound to bile acid monomers and micelles. Alteration of biliary lipid secretion by orally administered bile acids is a major first step in the medical treatment of calculous biliary disease.

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References

  1. Hofmann AF: The enterohepatic circulation of bile acids.In Handbook of Physiology. Section on the Gastrointestinal System. Schultz SG (ed). Bethesda, Maryland, American Physiological Society (in press)

  2. Hofmann AF: The secretion of bile: An overview.In Handbook of Physiology. Section on the Gastrointestinal System. Schultz SG (ed). Bethesda, Maryland, American Physiological Society (in press)

  3. Hofmann AF, Roda A: Physicochemical properties of bile acids and their relationship to biological properties: An overview of the problem. J Lipid Res 25:1477–1489, 1984

    PubMed  Google Scholar 

  4. Hofmann AF, Mysels KJ: Bile salts as biological surfactants. Colloids Surfaces 30:145–173, 1988

    Google Scholar 

  5. Erlinger S: Bile flow.In The Liver: Biology and Pathobiology. Arias IM, Jakoby WB, Popper H, Schachter D, Shafritz DA (eds). New York, Raven Press, 1988, pp 643–661

    Google Scholar 

  6. Miyairi M, Oshio C, Watanabe S, Smith CR, Yousef IM, Phillips MJ: Taurocholate accelerates bile canalicular contractions in isolated rat hepatocytes. Gastroenterology 87:788–792, 1984

    PubMed  Google Scholar 

  7. Watanabe S, Phillips MJ: Ca++ causes active contraction of bile canaliculi: Direct evidence from microinjection studies. Proc Natl Acad Sci USA 81:6164–6168, 1984

    PubMed  Google Scholar 

  8. Smith CR, Oshio C, Miyairi M, Katz H, Phillips MJ: Coordination of the contractile activity of bile canaliculi. Evidence from spontaneous contractions in vitro. Lab Invest 53:270–279, 1985

    PubMed  Google Scholar 

  9. Yoon YB, Hagey LR, Hofmann AF, Gurantz D, Michelotti EL, Steinbach JH: Effect of side-chain shortening on the physiological properties of bile acids: Hepatic transport and effect on biliary secretion of 23-nor-ursodeoxycholate in rodents. Gastroenterology 90:837–852, 1986

    PubMed  Google Scholar 

  10. Palmer KR, Gurantz D, Hofmann AF, Clayton LM, Hagey LR, Cecchetti S: Hypercholeresis induced by nor-chenodeoxycholate in the biliary fistula rodent. Am J Physiol 252:G219-G228, 1987

    PubMed  Google Scholar 

  11. Gurantz D, Schteingart CD, Hagey LR, Steinbach JH, Grotmol T, Hofmann AF: Hypercholeresis induced by unconjugated bile acid infusion is mediated by biliary secretion and not hepatocyte retention of unconjugated bile acids. (submitted)

  12. O'Maille ERL, Hofmann AF: Relatively high biliary secretory maximum for non-micelle-forming bile acid: Possible significance for mechanism of secretion. Q J Exp Physiol 71:475–482, 1986

    PubMed  Google Scholar 

  13. van Berge Henegouwen GP, Hofmann AF: Nocturnal gallbladder storage and emptying in gallstone patients and healthy subjects. Gastroenterology 75:879–885, 1978

    PubMed  Google Scholar 

  14. Shiffman ML, Carithers RL Jr, Moore EW: Bile secretion following orthotopic liver transplantation (OLT): All bile flow is dependent upon bile acid secretion. Hepatology 8:1454, 1988 (abstract)

    Google Scholar 

  15. Dumont M, Erlinger S, Uchman S: Hypercholeresis induced by ursodeoxycholic acid and 7-ketolithocholic acid in the rat. Possible role of bicarbonate transport. Gastroenterology 79:82–89, 1980

    PubMed  Google Scholar 

  16. Lake JR, Renner EL, Scharschmidt BF, Cragoe EJ Jr, Hagey LR, Lambert KJ, Gurantz D, Hofmann AF: Inhibition of Na+/H+ exchange in the rat is associated with decreased ursodeoxycholate hypercholeresis, decreased secretion of unconjugated ursodeoxycholate, and increased ursodeoxycholate glucuronidation. Gastroenterology 95:454–463, 1988

    PubMed  Google Scholar 

  17. Josephson B: The circulation of the bile acids in connection with their production, conjugation, and excretion. Physiol Rev 21:463–486, 1941

    Google Scholar 

  18. Jansen PL, Groothuis M, Peters WH, Meijer DF: Selective hepatobiliary transport defect for organic anions and neutral steroids in mutant rats with hereditary-conjugated hyperbil-irubinemia. Hepatology 7:71–76, 1987

    PubMed  Google Scholar 

  19. Oude Elferink RPJ, de Haan J, Lambert KJ, Hagey LR, Hofmann AF, Jansen PLM: Selective hepatobiliary transport of nordeoxycholate side chain conjugated in mutant rats with a canalicular transport defect. Hepatology 9:861–865, 1989

    PubMed  Google Scholar 

  20. Coleman R: Biochemistry of bile secretion. Biochem J 244:249–261, 1987

    PubMed  Google Scholar 

  21. Carey MC, Cohen DE: Biliary transport of cholesterol in vesicles, micelles and liquid crystals.In Bile Acids and the Liver. Paumgartner G, Stiehl A, and Gerok W (eds). Lancaster, UK, MTP Press, 1987, pp 287–384

    Google Scholar 

  22. Crawford JM, Berken CA, Gollan JL: Role of the hepatocyte microtubular system in the excretion of bile salts and biliary lipid: Implications for intracellular vesicular transport. J Lipid Res 29:144–156, 1988

    PubMed  Google Scholar 

  23. Sakisaka S, Ng OC, Boyer JL: Tubulovesicular transcytotic pathway in isolated rat hepatocyte couplets in culture. Effect of colchicine and taurocholate. Gastroenterology 95:793–804, 1988

    PubMed  Google Scholar 

  24. Crawford JM, Gollan JL: Transcellular lipid transport studied by fluorescence microscopy of hepatocytes: Taurocholate recruits NBD-ceramide for excretion into bile. Hepatology 8:1260, 1988 (abstract)

    Google Scholar 

  25. Coleman R, Rahman K, Bellringer ME, Carrella M: Biliary lipid secretion and its control.In Bile Acids in Health and Disease. Northfield T, Jazrawi R, Zentler-Munro P (eds). Boston, Kluwer Academic Publishers, 1988, pp 43–60

    Google Scholar 

  26. Takikawa H, Ookhtens M, Stolz A, Kaplowitz N: Cyclical oxidation-reduction of the C3 position on bile acids catalyzed by 3α-hydroxy-steroid dehydrogenase. II. Studies in the prograde and retrograde single-pass perfused rat liver and inhibition by indomethacin. J Clin Invest 80:861–866, 1987

    PubMed  Google Scholar 

  27. Roda A, Aldini R, Grigolo B, Simoni P, Roda E, Pellicciari R, Lenzi PL, Natalini B: 23-Methyl-3α,7β-dihydroxy-5β-cholan-24-oic acid: Dose-response study of biliary secretion in rat. Hepatology 8:1571–1576, 1988

    PubMed  Google Scholar 

  28. Cohen BI, Hofmann AF, Mosbach EH, Stenger RJ, Rothschild MA, Hagey LR, Yoon YB: Differing effects of nor-ursodeoxycholic or ursodeoxycholic acid on hepatic histology and bile acid metabolism in the rabbit. Gastroenterology 91:189–197, 1986

    PubMed  Google Scholar 

  29. Higuchi WI, Arakawa M, Lee PH, Noro S: Simple micellemixed micelle coexistence equilibria for the taurocholate-, taurochenodeoxycholate- and tauroursodeoxycholate-lecithin systems. J Colloid Interface Sci 119:30–37, 1987

    Google Scholar 

  30. Rege RV, Moore EM: Pathogenesis of calcium-containing gallstones. Canine ductular bile, but not gallbladder bile, is supersaturated with calcium carbonate. J Clin Invest 77:21–26, 1986

    PubMed  Google Scholar 

  31. Schaad UB, Wedgwood-Krucko J, Tschaeppeler H: Reversible ceftriaxone-associated biliary pseudolithiasis in children. Lancet 2:1411–1413, 1988

    PubMed  Google Scholar 

  32. Lira MA, McRoberts J, Schteingart CD, Lambert KJ, Steinbach JH, Hofmann AF: Hexose absorption by the biliary ductular epithelium: Evidence for two transport systems. Hepatology 8:1452, 1988 (abstract)

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, University of California, San Diego, T-013, La Jolla, California

    Alan F. Hofmann

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  1. Alan F. Hofmann
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Supported by NIH grants DK 21506 and DK 32130 as well as a grant-in-aid from the Falk Foundation, e.v.

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Hofmann, A.F. Current concepts of biliary secretion. Digest Dis Sci 34 (Suppl 12), S16–S20 (1989). https://doi.org/10.1007/BF01536657

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  • DOI: https://doi.org/10.1007/BF01536657

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