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Mechanisms of Bile Secretion and Hepatic Transport

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Book cover Physiology of Membrane Disorders

Abstract

Bile is a complex aqueous secretion that is elaborated by the liver of all vertebrate species, stored in the gallbladder, and discharged into the common hepatic duct and intestine. Its primary source is formed from transport processes in the liver parenchymal cell. This hepatic bile originates at the bile canaliculus (Fig. 1) but can be modified by absorption or secretion at more distal sites along the bile ductules and ducts (Fig. 2). Not all of these transport phenomenon are clearly understood but together they generate an isosmotic electrolyte solution into which a variety of organic and inorganic solutes are also excreted. (Table I) These solutes comprise 5% of the weight of bile by volume in man, and include mixed lipid micelles composed of bile acids, cholesterol, and phospholipid, as well as amino acids, hormones, enzymes, metals, vitamins, prophyrins, and other miscellaneous endogenous and exogenous drugs, xenobiotics, and toxins.

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References

  1. Brauer, R. W. 1959. Mechanisms of bile secretion. J. Am. Med. Assoc. 169: 1462–1466.

    PubMed  CAS  Google Scholar 

  2. Forker, E. L. 1977. Mechanisms of hepatic bile formation. Annu. Rev. Physiol. 39: 323–347.

    PubMed  CAS  Google Scholar 

  3. Javitt, N. B. 1976. Hepatic bile formation. N. Engl. J. Med. 295: 1464–1469, 1511–1516.

    Google Scholar 

  4. Boyer, J. L. 1980. New concepts of mechanisms of hepatocyte bile formation. Physiol. Rev. 60: 303–326.

    PubMed  CAS  Google Scholar 

  5. Reichen, J., and G. Paumgartner. 1980. Excretory function of the liver. In: Liver and Biliary Tract Physiology. N. B. Javitt, ed. University Park Press, Baltimore, pp. 103–150.

    Google Scholar 

  6. Paumgartner, G., and D. Paumgartner. 1982. Current concepts of bile formation. Prog. Liver Dis. 7: 207–220.

    PubMed  CAS  Google Scholar 

  7. Blitzer, B. L., and J. L. Boyer. 1982. Cellular mechanisms of bile formation. Gastroenterology 82: 346–357.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  9. Scharschmidt, B. F. 1982. Bile formation and cholestasis, metabolism and enterohepatic circulation of bile acids, and gallstone formation. In: Hepatology: A Textbook of Liver Disease. D. Zakem and T. D. Boyer, eds. Saunders, Philadelphia, pp. 297–351.

    Google Scholar 

  10. Graf, J. 1983. Canalicular bile salt independent bile formation: Concepts and clues from electrolyte transport in rat liver. Am. J. Physiol. 7: 233–246.

    Google Scholar 

  11. Smith, R. L. 1973. The Excretory Function of Bile: The Elimination of Drugs and Toxic Substances in Bile. Chapman amp; Hall, London.

    Google Scholar 

  12. Levine, W. G. 1981. Biliary excretion of drugs and other xenobiotics. Prog. Drug Res. 25: 362–420.

    Google Scholar 

  13. Hofmann, A. F. 1976. The enterohepatic circulation of bile acids in man. Adv. Intern. Med. 21: 501–534.

    PubMed  CAS  Google Scholar 

  14. Carey, M. C. 1982. The enterohepatic circulation. In: The Liver: Biology andPathobiology. I. Arias, H. Popper, D. Schacter, and D. A. Schafritz, eds. Raven Press, New York. pp. 429–465.

    Google Scholar 

  15. Lemaitre-Coelho, I., G. D. F. Jackson, and J. P. Vaerman. 1977. Rat bile as a convenient source of secretory Ig A and free secretory component. Eur. J. Immunol. 7: 588–590.

    PubMed  CAS  Google Scholar 

  16. Wheeler, H. O. 1968. Water and electrolytes in bile. In: Hand-book of Physiology, Section 6. C. F. Code, ed. American Physio-logical Society, Washington, D.C. pp. 2409–2431.

    Google Scholar 

  17. Rundle, F. F., B. Robson, and M. Middleton. 1955. Bile drainage after cholecystectomy in man, with some observations on biliary fistula. Surgery 37: 903–910.

    PubMed  CAS  Google Scholar 

  18. Boyer, J. L., and J. R. Bloomer. 1974. Canalicular bile secretion in man: Studies utilizing the biliary clearance of 14C-mannitol. J. Clin. Invest. 54: 773–781.

    PubMed  CAS  Google Scholar 

  19. Blouin, A., R. P. Bolender, andE. R. Weibel. 1977. Distribution of organelles and membranes between hepatocytes and non- hepatocytes in the rat liver parenchyma: A sterological study. J. Cell Biol. 72: 441–455.

    PubMed  CAS  Google Scholar 

  20. Evans, W. H. 1980. A biochemical dissection of the functional polarity of the plasma membrane of the hepatocyte. Biochim. Biophys. Acta 604: 27–64.

    PubMed  CAS  Google Scholar 

  21. Boyer, J. L., R. M. Allen, and O.-C. Ng. 1983. Biochemical separation of Na+, K + -ATPase from a “purified” light density, “canalicular” enriched plasma membrane fraction from rat liver. Hepatology 3: 18–28.

    PubMed  CAS  Google Scholar 

  22. Inoue, M., R. Kinne, T. Tran, L. Biempica, and I. M. Arias. 1983. Rat liver canalicular membrane vesicles. J. Biol. Chem, 258: 5183–5188.

    PubMed  CAS  Google Scholar 

  23. Meier, P. J., E. S. Sztul, A. Reuben, and J. L. Boyer. 1984. Structural and functional polarity of canalicular and basolateral plasma membrane vesicles isolated in high yield from rat liver. J. Cell Biol 98: 991–1000.

    PubMed  CAS  Google Scholar 

  24. Renston, R. H., A. L. Jones, W. D. Christiansen, and G. T. Hradek. 1980. Evidence for a vesicular transport mechanism in hepatocytes for biliary secretion of immunoglobulin A. Science 208: 1276–1278.

    PubMed  CAS  Google Scholar 

  25. LaRusso, N. F., and S. Fowler. 1979. Coordinate secretion of acid hydrolases in rat bile—Hepatocyte exocytosis of lysosomal protein? J. Clin. Invest. 64: 948–954.

    PubMed  CAS  Google Scholar 

  26. Jones, A. L., D. L. Schmucker, J. S. Mooney, R. K. Ockner, and R. D. Adler. 1979. Alterations in hepatic pericanalicular cytoplasm during enhanced bile secretory activity. Lab. Invest. 40: 512–517.

    PubMed  CAS  Google Scholar 

  27. Phillips, M. J., M. Oda, E. Mak, M. M. Fisher, and K. N. Jeejeebhoy. 1975. Microfilament dysfunction as a possible cause of intrahepatic cholestasis. Gastroenterology 69: 48–58.

    PubMed  CAS  Google Scholar 

  28. Elias, E., Z. Hruban, J. B. Wade, and J. L. Boyer. 1980. Phal- loidin-induced cholestasis, a microfilament-mediated change in junctional complex permeability. Proc. Natl. Acad. Sci. USA 77: 2229–2233.

    PubMed  CAS  Google Scholar 

  29. DeBrabander, M., J. C. Wanson, R. Mosselmans, G. Geuns, and P. Drochmans. 1978. Effects of antimicrotubular compounds on monolayer cultures of adult rat hepatocytes. Biol. Cell. 31: 127–140.

    Google Scholar 

  30. Dubin, M., M. Maurice, G. Feldmann, and S. Erlinger. 1980. Influence of colchicine and phalloidin on bile secretion and hepatic ultrastructure in the rat. Gastroenterology 79: 646–654.

    PubMed  CAS  Google Scholar 

  31. Oshio, C., and M. J. Phillips. 1981. Contractility of bile canaliculi: Implications for liver function. Science 212: 1041–1042.

    PubMed  CAS  Google Scholar 

  32. Phillips, M. J., C. Oshio, M. Miyairi, and C. R. Smith. 1983. Intrahepatic cholestasis as a canalicular motility disorder—Evidence using cytochalasin. Lab. Invest. 48: 205–211.

    PubMed  CAS  Google Scholar 

  33. Boyer, J. L. 1983. Tight junctions in normal and cholestatic liver: Does the paracellular pathway have functional significance? Hepatology 3: 614–617.

    PubMed  CAS  Google Scholar 

  34. Lagarde, S., E. Elias, J. B. Wade, and J. L. Boyer. 1981. Structural heterogeneity of hepatocyte “tight junctions”: A quantitative analysis. Hepatology 1: 193–203.

    PubMed  CAS  Google Scholar 

  35. Easter, D. W., J. B. Wade, and J. L. Boyer. 1983. Structural integrity of hepatocyte tight junctions. J. Cell Biol. 96: 745–749.

    PubMed  CAS  Google Scholar 

  36. Bradley, S. E., and R. Herz. 1978. Permselectivity of biliary canalicular membrane in rats: Clearance probe analysis. Am. J. Physiol. 235: E570–E576.

    PubMed  CAS  Google Scholar 

  37. Rappaport, A. M. 1973. The microcirculatory hepatic unit. Mi- crovasc. Res. 6: 212-228.

    Google Scholar 

  38. Miller, D. L., C. S. Zanolli, and J. J. Gumucio. 1979. Quantitative morphology of sinusoids of the hepatic acinusquantimet analysis of rat liver. Gastroenterology 76: 965–969.

    PubMed  CAS  Google Scholar 

  39. Gumucio, J. J., C. Balabaud, D. L. Miller, L. J. Mason, H. D. Appelman, T. J. Stoecker, and D. R. Franzblau. 1978. Bile secretion and liver cell heterogeneity in the rat. J. Lab. Clin. Med. 91: 350–362.

    PubMed  CAS  Google Scholar 

  40. Gumucio, J. J., and D. L. Miller. 1981. Functional implications of liver cell heterogeneity. Gastroenterology 80: 393–403.

    PubMed  CAS  Google Scholar 

  41. Jungerman, K., and N. Katz. 1982. Functional hepatocellular heterogeneity. Hepatology 2: 385–395.

    Google Scholar 

  42. Brauer, R. W., G. F. Leong, R. F. McElroy, and R. J. Holloway. 1954. Mechanisms of bile secretion: Effect of perfusion pressure and temperature on bile flow and secretion pressure. Am. J. Physiol. 177: 103–112.

    PubMed  CAS  Google Scholar 

  43. Bizard, G. 1965. Enzyme inhibitors and biliary secretion. In: The Biliary System. W. Taylor, ed. Blackwell, Oxford, pp. 315–324.

    Google Scholar 

  44. Moore, E. W., and J. M. Dietschy. 1964. Na and K activity coefficients in bile and bile salts determined by glass electrodes. Am. J. Physiol. 206: 1111–1117.

    PubMed  CAS  Google Scholar 

  45. Wheeler, H. O., and O. L. Ramos. 1960. Determinants of the flow and composition of bile in the unanesthetized dog during constant infusions of sodium taurocholate. J. Clin. Invest. 39: 161–170.

    PubMed  CAS  Google Scholar 

  46. Sperber, I. 1963. Biliary secretion and choleresis. In: Proc. 1st Int. Pharmacol. Meet. Volume 4. Pergamon Press, Elmsford, N.Y. pp. 137–143.

    Google Scholar 

  47. Sperber, I. 1965. Biliary secretion of organic anions and its influence on bile flow. In: The Biliary System. W. Taylor, ed. Blackwell, Oxford, pp. 457–467.

    Google Scholar 

  48. Wheeler, H. O., E. D. Ross, and S. E. Bradley. 1968. Canalicular bile production in dogs. Am. J. Physiol. 214: 866–874.

    PubMed  CAS  Google Scholar 

  49. Preisig, R., H. L. Cooper, and H. O. Wheeler. 1962. The relationship between taurocholate secretion rate and bile production in the unanesthetized dog during cholinergic blockade and during secretin administration. J. Clin. Invest. 41: 1152–1162.

    PubMed  CAS  Google Scholar 

  50. Forker, E. L. 1968. Bile formation in guinea pigs: Analysis with inert solutes of graded molecular radius. Am. J. Physiol. 215: 56 - 62.

    PubMed  CAS  Google Scholar 

  51. Strasberg, S. M., R. G. Ilson, K. H. Siminovitch, D. Brenner, and J. E. Palaheimo. 1975. Analysis of the components of bile flow in the rhesus monkey. Am. J. Physiol. 228: 115–121.

    PubMed  CAS  Google Scholar 

  52. Strasberg, S. M., R. G. Ilson, and C. N. Petrunka. 1982. 14C- erythritol clearance and canalicular bile acid independent flow in the baboon. Am. J. Physiol. 242: G475–G480.

    Google Scholar 

  53. Barnhart, J. L., and B. Combes. 1978. Erythritol and mannitol clearances with taurocholate and secretin induced choleresis. Am. J. Physiol. 234: E146–E156.

    PubMed  CAS  Google Scholar 

  54. Nicholls, R. J. 1979. Biliary mannitol clearance and bile salt output before and during secretin choleresis in the dog. Gastroenterology 76: 983–987.

    PubMed  CAS  Google Scholar 

  55. Lewis, M. H., A. L. Baker, J. M. Dhorajiwala, and A. R. Moossa. 1981. Secretin enhances 14C-erythritol clearance in un-anesthetized dogs. Dig. Dis. Sci. 27: 57–64.

    Google Scholar 

  56. Smith, N. D., and J. L. Boyer. 1982. Permeability characteristics of bile duct in the rat. Am. J. Physiol. 242: G52–G57.

    PubMed  CAS  Google Scholar 

  57. Javitt, N. B. 1977. Bile formation. In: Chemistry and Physiology of Bile Pigments. P. D. Berk and N. Berlin, eds. Fogarty Int. Cent. Proc. No. 35. U.S. Government Printing Office. Bethesda. pp. 377–382.

    Google Scholar 

  58. Lorenzini, I., T. liter, P. Meier, and J. L. Boyer. 1982. Taurochenodeoxycholic acid (TCDA) stimulates hepatic uptake of 3H-methoxyinulin (3HMI) into membrane bound compartments. Hepatology 2: 737a.

    Google Scholar 

  59. Anwer, M.S., and J. L. Barnhart. 1982. Polyethylene glycol-900 (PEG-900): A possible marker for paracellular water movement. Hepatology 2: 688a.

    Google Scholar 

  60. Krell, H., H. Hoke, and E. Pfaff. 1982. Development of intrahepatic cholestasis by a-naphthylisothiocyanate in rats. Gastroenterology 82: 507–514.

    PubMed  CAS  Google Scholar 

  61. Graf, J., and M. Peterlik. 1975. Mechanism of transport of inorganic ions into bile. In: The Hepatobiliary System—Fundamental and Pathological Mechanisms. W. Taylor, ed. Plenum Press, New York. pp. 43–58.

    Google Scholar 

  62. Schiff, M. 1890. Gallenbildung, abhangig non der Aufsaugung der Gallenstoffe. Pfluegers Arch. Gesamte Physiol. 3: 598–613.

    Google Scholar 

  63. Wheeler, H. O. 1972. Secretion of bile acids by the liver and their role in the formation of hepatic bile. Arch. Intern. Med. 130: 533–541.

    PubMed  CAS  Google Scholar 

  64. Klaassen, C. D. 1972. Species differences to the choleretic response to bile salts. J. Physiol. (London) 224: 259–269.

    CAS  Google Scholar 

  65. Vonk, R. J., P. Jekel, and D. K. F. Meijer. 1975. Choleresis and hepatic transport mechanism. Naunyn-Schmiedebergs Arch. Pharmacol. 290: 375–387.

    CAS  Google Scholar 

  66. O’Maille, E. R. L. 1980. The influence of micelle formation on bile secretion. Physiol. (London) 302: 107 - 120.

    Google Scholar 

  67. Sewell, R. B., N. E. Hoffman, R. A. Smallwood, and S.Cock- bain. 1980. Bile acid structure and bile formation: A comparison of hydroxy and keto bile acids. Am. J. Physiol. 238: G10–G17.

    PubMed  CAS  Google Scholar 

  68. O’Maille, E. R. L., M. S. Anwer, A. F. Hofmann, E. B. Ljunge, and R. G. Danzinger. 1982. Side chain charge: A key determinant of hepatic bile acid transport. Gastroenterology 82: 1140a.

    Google Scholar 

  69. Javitt, N. B., and S. Emerman. 1968. Effect of sodium taurolithocholate on bile flow and bile acid excretion. J. Clin. Invest. 47: 1002–1014.

    PubMed  CAS  Google Scholar 

  70. Layden, T. J., and J. L. Boyer. 1977. Taurolithocholate induced cholestasis: Taurocholate, but not dehydrocholate, reverses cholestasis and bile canalicular membrane injury. Gastroenterology 73: 120–128.

    PubMed  CAS  Google Scholar 

  71. Kitani, K., and S. Kanai. 1981. Biliary transport maximum of tauroursodeoxycholate is twice as high as that of taurocholate in the rat. Life Sci. 29: 260–275.

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  73. Scharschmidt, B. F., E. B. Keefe, D. Vessey, N. M. Blankenship, and R. K. Ochner. 1981. In vitro effect of bile salts on rat liver plasma membrane lipid fluidity and ATPase activity. Hepatology 1: 137–145.

    PubMed  CAS  Google Scholar 

  74. Baker, A. L., R. A. B. Wood, A. R. Moossa, and J. L. Boyer. 1978. Sodium taurocholate modifies the bile acid-independent fraction of canalicular bile flow in the rhesus monkey. J. Clin. Invest. 64: 312 - 320.

    Google Scholar 

  75. Boyer, J. L., and D. Reno. 1975. Properties of (Na+ -K +) activated ATPase in rat liver plasma membranes enriched with bile canaliculi. Biochim. Biophys. Acta 401: 59–72.

    PubMed  CAS  Google Scholar 

  76. Nemchausky, B., D. Reno, and J. L. Boyer. 1975. Synthetic and naturally occurring bile salts—Modifiers of ATPase activity in canalicular enriched liver plasma membrane. Clin. Res. 23: 254a.

    Google Scholar 

  77. Wannagat, F. J., R. D. Alder, and R. K. Ochner. 1978. Bile acid- induced increase in bile acid independent flow and plasma membrane Na+, K +-ATPase in the rat liver. J. Clin. Invest. 61: 297–307.

    PubMed  CAS  Google Scholar 

  78. Accatino, L., A. Contreras, E. Berdichevsky, and C. Qunitana. 1981. The effect of complete biliary obstruction on bile secretion: Studies on the mechanisms of post cholestatic choleresis in the rat. J. Lab. Clin. Med. 97: 525–534.

    PubMed  CAS  Google Scholar 

  79. Miyai, K., and W. G. Hardison. 1979. Bile duct ligation vs. retention of bile: Pericanalicular microfilaments form bundles only with bile duct ligation. Gastroenterology 76: 1292a.

    Google Scholar 

  80. Balabaud, C., K. A. Korn, and J. J. Gumucio. 1977. The assessment of the bile salt nondependent fraction of canalicular bile water in the rat. J. Lab. Clin. Med. 89: 393–399.

    PubMed  CAS  Google Scholar 

  81. Reichen, J., and G. Paumgartner. 1977. Relationship between bile flow and Na+,K +-adenosine triphosphatase in liver plasma membranes enriched in bile canaliculi. J. Clin. Invest. 60: 429–434.

    PubMed  CAS  Google Scholar 

  82. Layden, T. J., and J. L. Boyer. 1976. The effect of thyroid hormone on bile salt-independent bile flow and Na+,K + -ATPase activity in liver plasma membranes enriched in bile canaliculi. J. Clin. Invest. 57: 1009–1018.

    PubMed  CAS  Google Scholar 

  83. Simon, F. R., E. Sutherland, and L. A. Accatino. 1977. Stimulation of hepatic sodium and potassium-activated adenosine triphosphatase activity by phenobarbital—Its possible role in regulation of bile flow. J. Clin. Invest. 59: 849–861.

    PubMed  CAS  Google Scholar 

  84. LaRusso, N. F., M. G. Korman, N. E. Hoffman, and A. F. Hofmann. 1974. Dynamics of the enterohepatic circulation of bile acids: Postprandial serum concentrations of conjugates of cholic acid in health, cholecystectomized patients, and patients with bile acid malabsorption. N. Engl. J. Med. 291: 689–692.

    PubMed  CAS  Google Scholar 

  85. Angelin, B. O., I. Bjorkhem, K. Einarsson, and S. Ewerth. 1982. Hepatic uptake of bile acids in man—Fasting and postprandial concentrations of individual bile acids in portal venous and systemic blood serum. J. Clin. Invest. 70: 724–731.

    PubMed  CAS  Google Scholar 

  86. Ahlberg, J., B. Angelin, I. Bjorkhem, and K. Einarsson. 1979. Individual bile acids in portal venous and systemic blood of fasting man. Gastroenterology 73: 1377–1382.

    Google Scholar 

  87. Lindblad, L., K. Lundholm, and T. Schersten. 1977. Bile acid concentrations in systemic and portal serum in presumably normal man and in cholestatic and cirrhotic conditions. Scand. J. Gastroenterol. 12: 395–400.

    PubMed  CAS  Google Scholar 

  88. Olivecrona, T., and J. Sjovall. 1959. Bile acids in rat portal blood. Acta Physiol. Scand. 46: 284–290.

    PubMed  CAS  Google Scholar 

  89. Cronholm, T., and J. Sjovall. 1967. Bile acids in portal blood of rats fed different diets and cholestyramine. Eur. J. Biochem. 2: 375–383.

    PubMed  CAS  Google Scholar 

  90. Matern, S., and W. Gerok. 1979. Pathophysiology of the enterohepatic circulation. Rev. Physiol. Biochem. Pharmacol. 85: 126–204.

    Google Scholar 

  91. Mok, H. Y. I., K. von Bergman, and S. M. Grundy. 1980. Ki¬netics of the enterohepatic circulation during fasting: Biliary lipid secretion and gallbladder storage. Gastroenterology 78: 1023–1033.

    PubMed  CAS  Google Scholar 

  92. Rudman, D., and F. E. Kendall. 1957. Bile acid content of human serum. II. The binding of cholanic acids by human plasma proteins. J. Clin. Invest. 36: 538–542.

    PubMed  CAS  Google Scholar 

  93. Hoffman, N. E., J. H. Iser, R. A. Smallwood. 1975. Hepatic bile acid transport: Effect of conjugation and position of hydroxyl groups. Am. J. Physiol. 229: 298–302.

    PubMed  CAS  Google Scholar 

  94. Aldini, R., A. Roda, A. M. Morselli, G. Cappelleri, E. Roda, and L. Barbara. 1982. Hepatic bile acid uptake: Effect of conjugation, hydroxyl and keto groups, and albumin binding. J. Lipid Res. 23: 1167–1173.

    PubMed  CAS  Google Scholar 

  95. Iga, T., and C. D. Klaassen. 1982. Hepatic extraction of bile acids in rats. Biochem. Pharmacol. 31: 205–209.

    PubMed  CAS  Google Scholar 

  96. Kramer, W., H.-P. Buscherg, W. Gerok, andG. Kurz. 1979. Bile salt binding to serum components: Taurocholate incorporation into high-density lipoproteins revealed by photoaffinity labelling. Eur. J. Biochem. 102: 1–9.

    PubMed  CAS  Google Scholar 

  97. Forker, E. L., and B. A. Luxon. 1981. Albumin helps mediate removal of taurocholate by rat liver. J. Clin. Invest. 67: 1517–1522.

    PubMed  CAS  Google Scholar 

  98. Layden, T. J., and J. L. Boyer. 1978. Influence of bile acids on bile canalicular size. Lab. Invest. 39: 110–119.

    PubMed  CAS  Google Scholar 

  99. Groothuis, G. M. M., M. Hardonk, K. P. T. Keulemans, P. Nieuwenhuis, and D. K. F. Meijer. 1982. Autoradiographic and kinetic demonstration of acinar heterogeneity of taurocholate transport. Am. J. Physiol. 243: G455–G462.

    PubMed  CAS  Google Scholar 

  100. Jones, A. L., G. T. Hradek, R. H. Renston, K. W. Wong, G. Karlaganis, and G. Paumgartner. 1980. Autoradiographic evidence for hepatic lobular concentration gradient of bile acid derivative. Am. J. Physiol. 238: G233–G237.

    PubMed  CAS  Google Scholar 

  101. Suchy, F. J., W. F. Balistreri, J. Hung, P. Miller, and S. A. Garfield. 1983. Intracellular bile acid transport in rat liver as visualized by electron microscope autoradiography using a bile acid analogue. Am. J. Physiol. 245: G681–G689.

    PubMed  CAS  Google Scholar 

  102. Elias, E., and J. L. Boyer. 1979. Mechanisms of intrahepatic cholestasis. Prog. Liver Dis. 6: 457–470.

    PubMed  CAS  Google Scholar 

  103. Reichen, J., and G. Paumgartner. 1975. Kinetics of taurocholate uptake by the perfused rat liver. Gastroenterology 68: 132–136.

    PubMed  CAS  Google Scholar 

  104. Glasinovic, J.-C., M. Dumont, M. Duval, and S. Erlinger. 1975. Hepatocellular uptake of taurocholate in the dog. J. Clin. Invest. 55: 419–426.

    CAS  Google Scholar 

  105. Reichen, J., and G. Paumgartner. 1976. Uptake of bile acids by perfused rat liver. Am. J. Physiol. 231: 734–742.

    PubMed  CAS  Google Scholar 

  106. Schwartz, L. R., R. Burr, M. Schwenk, E. Pfaff, and H. Greim. 1975. Uptake of taurocholic acid into isolated rat liver cells. Eur. J. Biochem. 55: 617–623.

    Google Scholar 

  107. Anwer, M. S., and D. Hegner. 1978. Effect of Na+ on bile acid uptake by isolated rat hepatocytes. Hoppe-Seylers Z. Physiol. Chem. 359: 181–192.

    PubMed  CAS  Google Scholar 

  108. Blitzer, B. L., S. L. Ratoosh, C. B. Donovan, and J. L. Boyer. 1982. Effects of inhibitors of Na+-coupled ion transport on bile acid uptake by isolated rat hepatocytes. Am. J. Physiol. 243: G48–G53.

    PubMed  CAS  Google Scholar 

  109. Scharschmidt, B. F., and J. E. Stephens. 1981. Transport of sodium, chloride, and taurocholate by cultured rat hepatocytes. Proc. Natl. Acad. Sci. USA 78: 986–990.

    PubMed  CAS  Google Scholar 

  110. von Dippe, P., and D. Levy. 1983. Characterization of the bile acid transport system in normal and transformed hepatocytes— Photoaffinity labelling of the taurocholate carrier proteins. J. Biol. Chem. 258: 8896–8901.

    Google Scholar 

  111. Abberger, H., U. Bickel, H. P. Buscher, K. Fuchte, W. Gerok, W. Krammer, and G. Kurz. 1981. Transport of bile acids: Lipoproteins, membrane polypeptides and cytosolic proteins as carriers. In: Bile Acids and Lipids. G. Paumgartner, A. Stiehl, and W. Gerok, eds. MTP Press, Lancaster, pp. 233–246.

    Google Scholar 

  112. Inoue, M., R. Kinne, T. Tran, and I. M. Arias. 1982. Taurocho- late transport by rat liver sinusoidal membrane vesicles: Evidence for sodium cotransport. Hepatology 2: 572–579.

    PubMed  CAS  Google Scholar 

  113. Duffy, M. C., B. L. Blitzer, and J. L. Boyer. 1983. Direct determination of the driving forces for taurocholate uptake into rat liver plasma membrane vesicles. J. Clin. Invest. 72: 1470–1481.

    PubMed  CAS  Google Scholar 

  114. Van Dyke, R. W., J. E. Stephens, and B. F. Scharschmidt. 1982. Bile acid transport in cultured rat hepatocytes. Am. J. Physiol. 243: G484–G492.

    PubMed  Google Scholar 

  115. Meier, P. J., A. S. Meier-Abt, C. Barrett, and J. L. Boyer. 1984. Mechanisms of taurocholate transport in canalicular and basolateral rat liver plasma membrane vesicles. J. Biol. Chem. 259: 10614–10622.

    PubMed  CAS  Google Scholar 

  116. Okishio, T., and P. P. Nair. 1966. Studies on bile acids: Some observations on the intracellular localization of major bile acids in rat liver. Biochemistry 5: 3662–3668.

    PubMed  CAS  Google Scholar 

  117. Boyer, J. L., M. Itabashi, and Z. Hruban. 1979. Formation of pericanalicular vacuoles during sodium dehydrocholate choleresis—A mechanism for bile acid transport: In: The Liver: Quantitative Aspects of Structure and Function. R. Preisig and J. Bircher, eds. Editio Cantor Aulendorf, Berne, pp. 163–178.

    Google Scholar 

  118. Reichen, J., M. D. Berman, and P. D. Berk. 1981. The role of microfilaments and of microtubules in taurocholate uptake by isolated rat liver cells. Biochim. Biophys. Acta 643: 126–133.

    PubMed  CAS  Google Scholar 

  119. Reuben, A., R. M. Allen, and J. L. Boyer. 1983. Intrahepatic source of “biliary-like” bile acid-phospholipid-cholesterol micelles. In: Bile Acids and Cholesterol in Health and Disease. G. Paumgartner, A. Stiehl, and W. Gerok, eds. MTP Press, Lancaster. pp. 61–66.

    Google Scholar 

  120. Strange, R. C., R. Cramb, J. D. Hayes, and I. W. Percy-Robb. 1977. Partial purification of two lithocholic acid-binding proteins from rat liver 100,000g supernatants. Biochem. J. 165: 425–429.

    PubMed  CAS  Google Scholar 

  121. Strange, R. C., I. A. Nimmo, and I. W. Percy-Robb. 1977. Binding of bile acids by 100,000g supernatants from rat liver. Biochem. J. 162: 659–664.

    PubMed  CAS  Google Scholar 

  122. Kaplowitz, N. 1980. Physiological significance of glutathione S- transferases. Am. J. Physiol. 239: G439–G444.

    PubMed  CAS  Google Scholar 

  123. Sugiyama, Y., T. Yamada, and N. Kaplowitz. 1983. Newly identified bile acid binders in rat liver cytosol—Purification and comparison with glutathione transferases. J. Biol. Chem. 258: 3602–3607.

    PubMed  CAS  Google Scholar 

  124. Accatino, L., and F. R. Simon. 1976. Identification and characterization of a bile acid receptor in isolated liver surface membranes. J. Clin. Invest. 57: 496–508.

    PubMed  CAS  Google Scholar 

  125. Gonzalez, M., E. Sutherland, and F. R. Simon. 1979. Regulation of hepatic transport of bile salts: Effects of protein synthesis inhibition on excretion of bile salts and their binding to liver surface membrane fractions. J. Clin. Invest. 63: 684–694.

    PubMed  CAS  Google Scholar 

  126. Graf, J., and O. H. Peterson. 1978. Cell membrane potential and resistance in liver. J. Physiol. (London) 284: 105–126.

    CAS  Google Scholar 

  127. Rollins, D. E., J. W. Freston, andD. M. Woodbury. 1980. Transport of organic anions into liver cells and bile. Biochem. Pharmacol. 29: 1023–1028.

    PubMed  CAS  Google Scholar 

  128. Graf, J., A. Gautam, and J. L. Boyer. 1984. Isolated rat hepatocyte couplets: A primary secretory unit for electrophysiologic studies of bile secretory function. Proc. Natl. Acad. Sci. 81: 6516–6520.

    PubMed  CAS  Google Scholar 

  129. Inoue,M.,R. Kinne, J. Tran, and I.M. Arias. 1984. Taurocholate transport by rat liver canalicular membrane vesicles-evidence for the presence of an Na+-independent transport system. J. Clin. Invest. 73: 659–663.

    Google Scholar 

  130. Scharschmidt, B. F., and R. Schmid. 1978. The micellar sink: A quantitative assessment of the association of organic anions with mixed micelles and other macromolecular aggregates in rat bile. J. Clin. Invest. 62: 1122–1131.

    PubMed  CAS  Google Scholar 

  131. Tavoloni, N., J. S. Reed, and J. L. Boyer. 1978. Hemodynamic effects on determinants of bile secretion in isolated rat liver. Am. J. Physiol. 234: E584–E592.

    PubMed  CAS  Google Scholar 

  132. Reed, J. S., N. D. Smith, and J. L. Boyer. 1982. Hemodynamic effects on oxygen consumption and bile flow in isolated skate liver. Am. J. Physiol. 242: G313–G318.

    PubMed  CAS  Google Scholar 

  133. Reed,J.S.,N. D.Smith, and J. L. Boyer. 1982. Determinants of biliary secretion in isolated perfused skate liver. Am. J. Physiol. 242: G319–G325.

    Google Scholar 

  134. Erlinger, S., and D. Dhumeaux. 1974. Mechanism and control of secretion of bile water and electrolytes. Gastroenterology 66: 281–304.

    PubMed  CAS  Google Scholar 

  135. Keeffe, E. B., B. F. Scharschmidt, N. M. Blankenship, and R. K. Ockner. 1979. Studies of relationships among bile flow, liver plasma membrane Na+,K+-ATPase, and membrane microviscosity in the rat. J. Clin. Invest. 64: 1590–1598.

    CAS  Google Scholar 

  136. Shaw, H. M., and T. J. Heath. 1974. Regulation of bile formation in rabbits and guinea pigs. Q. J. Exp. Physiol. 53: 93–102.

    Google Scholar 

  137. Graf, J., and M. Peterlik. 1976. Quabain-mediated sodium uptake and bile formation by isolated perfused liver. Am. J. Physiol. 230: 876–885.

    PubMed  CAS  Google Scholar 

  138. Blitzer, B. L., and J. L. Boyer. 1978. Cytochemical localization of Na+K +-ATPase in the rat hepatocyte. J. Clin. Invest. 62: 1104–1108.

    PubMed  CAS  Google Scholar 

  139. Latham, P. S., and M. Kashgarian. 1979. The ultrastructural localization of transport ATPase in the rat liver at non-bile canalicular plasma membrane. Gastroenterology 76: 988–996.

    PubMed  CAS  Google Scholar 

  140. Poupon, R. E., and W. H. Evans. 1979. Biochemical evidence that Na+,K + -ATPase is located at the lateral region of the hepatocyte surface membrane. FEBS Lett. 108: 374–378.

    PubMed  CAS  Google Scholar 

  141. Scharschmidt, B. F., and E. B. Keeffe. 1981. Isolation of a rat liver plasma membrane fraction of probable canalicular origin— Preparative technique, enzymatic profile, composition, and solute transport. Biochim. Biophys. Acta 646: 369–381.

    PubMed  CAS  Google Scholar 

  142. Claret, M. 1979. Transport of ions in liver cells. In: Membrane Transport in Biology, Volume IVB. G. Giebisch, D.C. Tosteson, and H. H. Ussing, eds. Springer-Verlag, Berlin, pp. 899–920.

    Google Scholar 

  143. Dambach, G., and N. Friedmann. 1974. The effects of varying ionic composition of the perfusate on liver membrane potential, gluconeogenesis and cyclic AMP responses. Biochim. Biophys. Acta 332: 374–386.

    CAS  Google Scholar 

  144. Claret, B., M. Claret, and J. L. Mazet. 1973. Ionic transport and membrane potential of rat liver cells in normal and low chloride solutions. J. Physiol. (London) 230: 87–101.

    CAS  Google Scholar 

  145. Graf, J., and O. H. Petersen. 1974. Electrogenic sodium transport in mouse liver parenchymal cells. Proc. R. Soc. London Ser. B 187: 363–367.

    CAS  Google Scholar 

  146. van Rossum, G. D. V., and M. A. Russo,1981. Ouabain-resistant mechanism of volume control and the ultrastructural organization of liver slices recovering from swelling in vivo. J. Membr. Biol. 59: 191–209.

    Google Scholar 

  147. Haylett, D. G., and D. H. Jenkinson. 1972. Effects of nor-adrenaline on potassium efflux, membrane potential and electrolyte levels in tissue slices prepared from guinea pig liver. J. Physiol. (London) 225: 721–750.

    CAS  Google Scholar 

  148. Graf, J. 1976. Sodium pumping and bile secretion. In: The Liver: Quantitative Aspects of Structure and Function. R. Preisig, J. Bircher, and G. Paumgartner, eds. Edito Cantor, Aulendorf. pp. 370–385.

    Google Scholar 

  149. Sips, H. J., M. M. van Amelsvoort, and F. van Dam. 1980. Amino acid transport in plasma-membrane vesicles from rat liver—Characterization of L-alanine transport. Eur. J. Biochem. 105: 217–224.

    PubMed  CAS  Google Scholar 

  150. Ernst, S. A., and J. W. Mills. 1977. Basolateral plasma membrane localization of ouabain-sensitive sodium transport sites in the secretory epithelium of the avian salt gland. J. Cell Biol. 75: 74–94.

    PubMed  CAS  Google Scholar 

  151. Epstein, F. H. 1979. The shark rectal gland: A model for the active transport of chloride. Yale J. Biol. Med. 52: 517–523.

    CAS  Google Scholar 

  152. Eveloff, J., R. Kinne, E. Kinne-Saffran, H. Murer, P. Silva, F. Epstein, J. Stoff, and W. B. Kinter. 1978. Coupled sodium and chloride transport into plasma membrane vesicles prepared from dogfish rectal gland. Pfluegers Arch. 378: 87–92.

    CAS  Google Scholar 

  153. Frizzell, R. A., M. Field, and S. G. Schultz. 1979. Sodium- coupled chloride transport by epithelial tissues. Am. J. Physiol. 236: F1 - F8.

    PubMed  CAS  Google Scholar 

  154. Anwer, M. S., and D. Hegner. 1982. Importance of solvent drag and diffusion in bile acid-dependent bile formation: Ion sbustitution studies in isolated perfused rat liver. Hepatology 2: 580–586.

    PubMed  CAS  Google Scholar 

  155. Anwer, M. S., and D. Hegner. 1983. Role of inorganic electrolytes in bile acid-independent canalicular bile formation. Am. J. Physiol. 244: 116–124.

    Google Scholar 

  156. Van Dyke, R. W., J. E. Stephens, andB. F. Scharschmidt. 1982. Effect of ion substitution on bile formation by the isolated perfused rat liver. J. Clin. Invest. 70: 505–517.

    PubMed  Google Scholar 

  157. Arias, I. M., and M. Forgac. 1984. The sinusoidal domain of the plasma membrane of rat hepatocytes contains an amiloride-sensitive Na+/H+ antiport. J. Biol. Chem. 259: 5406–5408.

    PubMed  CAS  Google Scholar 

  158. Fuchs, R., J. Graf, M. Peterlick, and T. Thalhammer. 1984. Sodium-proton antiport in sinusoidal liver cell membrane. Hepatology 4: 761a.

    Google Scholar 

  159. Mosley, R. H., P. J. Meier, R. Knickelbein, P. S. Aronson, and J. L. Boyer. 1984. Evidence for Na+ -H + exchange in rat liver basolateral but not canalicular membrane vesicles. Hepatology 4: 1040a.

    Google Scholar 

  160. Williams, J. A., C. D.Withrow, and D. M. Woodbury. 1971. Effects of ouabain and diphenylhydantoin on transmembrane potentials, intracellular electrolytes, and cell pH of rat muscle and liver in vivo. J. Physiol. (London) 212: 101–115.

    CAS  Google Scholar 

  161. Scharschmidt, B. F., and R. W. Van Dyke. 1983. Mechanisms of hepatic electrolyte transport. Gastroenterology 85: 1199–1214.

    PubMed  CAS  Google Scholar 

  162. Meier, P. J., R. Knickelbein, R. H. Mosley, J. W. Dobbins, and J. L. Boyer. 1985. Evidence for carrier modiated C1:HC03 exchange in canalicular rat liver plasma membrane vesicles. J. Clin Invest. 75: 1256–1263.

    PubMed  CAS  Google Scholar 

  163. Hardison, W. G. M., and C. A. Wood. 1978. Importance of bicarbonate in bile salt-independent fraction of bile flow. Am. J. Physiol. 235: E158–E164.

    PubMed  CAS  Google Scholar 

  164. Klos, C., G. Paumgartner, and J. Reichen. 1979. Cation-anion gap and choleretic properties of rat bile. Am. J. Physiol. 236: E434–E440.

    PubMed  CAS  Google Scholar 

  165. Eberle, D., R. Clarke, and N. Kaplowitz. 1981. Rapid oxidation in vitro of endogenous and exogenous glutathione in bile of rats. J. Biol. Chem. 256: 2115–2117.

    PubMed  CAS  Google Scholar 

  166. Inoue, M., R. Kinne, T. Tran, and I. M. Arias. 1983. The mechanism of biliary secretion of reduced glutathione—Analysis of transport process in isolated rat-liver canalicular membrane vesicles. Eur. J. Biochem. 134: 467–471.

    PubMed  CAS  Google Scholar 

  167. Gregory, D. H., Z. R. Vlahcevic, M. F. Prugh, and T. Swell. 1978. Mechanism of secretion of biliary lipids: Role of a microtubular system in hepatocellular transport of biliary lipids in the rat. Gastroenterology 74: 93–100.

    PubMed  CAS  Google Scholar 

  168. Godfrey, P. P., L. Lembra, and R. Coleman. 1982. Effects of colchicine and vinblastine on output of proteins into bile. Biochem. J. 208: 153–157.

    PubMed  CAS  Google Scholar 

  169. Layden, T. J., E. Elias, and J. L. Boyer. 1978. Bile formation in the rat: The role of the paracellular shunt pathway. J. Clin. Invest. 62: 1375–1385.

    PubMed  CAS  Google Scholar 

  170. Boyer, J. L., E. Elias, and T. J. Layden. 1979. The paracellular pathway and bile formation. Yale J. Biol. Med. 52: 61–67.

    PubMed  CAS  Google Scholar 

  171. Wade, J. B., J. P. Revel, and V. A. DiScala. 1973. Effect of osmotic gradients on intercellular junctions of the toad bladder. Am. J. Physiol. 224: 407–415.

    PubMed  CAS  Google Scholar 

  172. DiBona, D. R., and M. M. Civian. 1973. Pathways for movement of ions and water across toad urinary bladder. I. Anatomic site of transepithelial shunt pathways. J. Membr. Biol. 12: 101–128.

    PubMed  CAS  Google Scholar 

  173. Graf, J. 1976. Some aspects of the role of cyclic AMP and calcium in bile formation: Studies in the isolated perfused rat liver. In: Stimulus Secretion Coupling in the Gastrointestinal Tract. M. Case and H. Goebell, eds. MTP, Lancaster, pp. 305–328.

    Google Scholar 

  174. Chenderovitch, J., E. Phocas, and M. Matureau. 1963. Effects of hypertonic solutions on bile formation. Am. J. Physiol. 205: 863–867.

    CAS  Google Scholar 

  175. Guzelian, P., and J. L. Boyer. 1974. Glucose reabsorption from bile: Evidence for a biliohepatic circulation. J. Clin. Invest. 53: 526–535.

    PubMed  CAS  Google Scholar 

  176. Owen, C. A. 1977. Isolated rat liver needs calcium to make bile. Proc. Soc. Exp. Biol. Med. 155: 314–317.

    PubMed  CAS  Google Scholar 

  177. Baker, A. L., and M. M. Kaplan. 1976. Effects of cholera entero- toxin, glucagon, and dibutyryl cyclic AMP on rat liver alkaline phosphatase, bile flow, and bile composition. Gastroenterology 70: 577–581.

    PubMed  CAS  Google Scholar 

  178. Poupon, R. E., M. L. Dol, M. Dumont, and S. Erlinger. 1978. Evidence against a physiological role of cAMP in choleresis in dogs and rats. Biochem. Pharmacol. 27: 2413–2416.

    PubMed  CAS  Google Scholar 

  179. Morris, T. Q. 1972. Choleretic responses to cyclic AMP and theophylline in the dog. Gastroenterology 62: 187a.

    Google Scholar 

  180. Barnhart, J. L., and B. Combes. 1975. Characteristics common to choleretic increments of bile induced by theophylline, glucagon, and SQ-2009 in the dog. Proc. Soc. Exp. Biol. Med. 150: 591–596.

    PubMed  CAS  Google Scholar 

  181. Klaassen, C. D. 1971. Does bile acid secretion determine bile production in rats? Am. J. Physiol. 220: 667–673.

    PubMed  CAS  Google Scholar 

  182. Macarol, V., T. Q. Morris, K. J. Baker, and S. E. Bradley. 1970. Hydrocortisone choleresis in the dog. J. Clin. Invest. 49: 1714–1723.

    PubMed  CAS  Google Scholar 

  183. Zsigmond, G., andB. Solymoss. 1974. Increased canalicular bile production induced by pregnenolone-16a-carbonitrile, spironolactone and Cortisol in rats. Proc. Soc. Exp. Biol. Med. 145: 631–635.

    PubMed  CAS  Google Scholar 

  184. Capron, J. P., M. Dumont, G. Feldmann, and S. Erlinger. 1977. Barbiturate-induced choleresis: Possible independence from microsomal enzyme induction. Digestion 15: 556–565.

    PubMed  CAS  Google Scholar 

  185. Chivrac, D., M. Dumont, and S. Erlinger. 1978. Lack of paral-lelism between microsomal enzyme induction and phenobarbital- induced hypercholeresis in the rat. Digestion 17: 516–525.

    PubMed  CAS  Google Scholar 

  186. Klaassen, C. D. 1969. Biliary flow after microsomal enzyme induction. J. Pharmacol. Exp. Ther. 168: 218–223.

    PubMed  CAS  Google Scholar 

  187. Gumucio, J. J., and V. C. Valdivieso. 1971. Studies on the mechanism of ethinylestradiol impairment of bile flow and bile salt excretion in the rat. Gastroenterology 61: 339–344.

    PubMed  CAS  Google Scholar 

  188. Simon, F. R., M. Gonzalez, E. Sutherland, L. Accatino, and R. A. Davis. 1980. Reversal of ethinyl estradiol-induced bile secretory failure with Triton WR-1339. J. Clin. Invest. 65: 851–860.

    PubMed  CAS  Google Scholar 

  189. Davis, R. A., F. Kern, R. Showalter, E. Sutherland, M. Sinensky, and F. R. Simon. 1978. Alterations of hepatic Na+,K + -ATPase and bile flow by estrogen-effects on liver surface membrane lipid structure and function. Proc. Natl. Acad. Sci. USA 75: 4130–4134.

    PubMed  CAS  Google Scholar 

  190. Kern, F. 1978. Effect of estrogens on the liver. Gastroenterology 75: 512–522.

    Google Scholar 

  191. Berr, F., F. R. Simon, and J. Reichen. 1984. Ethinylestradiol impairs Bile salt uptake and Na-K pump function of rat hepatocytes. Amer. J. Physiol. 247: 6437–6443.

    Google Scholar 

  192. Boyer, J. L., S. Lagarde, O. C. Ng, and R. Groszmann. 1981. Enhanced biliary regurgitation of 14C-sucrose (14C-S) and lanthanum (La+ +) in ethinyl estradiol (EE) treated rats following retrograde bile duct infusions—A possible mechanism for intra-hepatic cholestasis. Hepatology 1: 498a.

    Google Scholar 

  193. Preisig, R., H. Strebel, G. Egger, and V. Macarol. 1972. Effect of vasopressin on hepatocyte and ductual bile formation in the dog. Experientia 28: 1436–1437.

    PubMed  CAS  Google Scholar 

  194. Lauterburg, B., G. Paumgartner, and R. Preisig. 1975. Prostaglandin-induced choleresis in the rat. Experientia 31: 1191–1193.

    PubMed  CAS  Google Scholar 

  195. Kaminski, D. L., M. Ruwart, and L. L. Willman. 1974. The effect of prostaglandin Aj and E! on canine hepatic bile flow. Surg. Res. 18: 391–397.

    Google Scholar 

  196. Sokoloff, J., and R. N. Berk. 1973. The effect of prostaglandin E2 on bile flow and the biliary excretion of iopanoic acid. Invest. Radiol. 8: 9–12.

    PubMed  CAS  Google Scholar 

  197. Karup, N., J. A. Larsen, and A. Munck. 1976. Secretin like choleretic effects of prostaglandin E1 and E2 in cats. J. Physiol. (London) 254: 813–820.

    Google Scholar 

  198. Larsen, J. A., and K. D. Christensen. 1978. Insulin-stimulated bile formation in cats. Acta Physiol. Scand. 102: 301–309.

    PubMed  CAS  Google Scholar 

  199. Snow, J. R., and R. S. Jones. 1978. The effect of insulin on bile salt-independent canalicular secretion. Surgery 83: 458–463.

    PubMed  CAS  Google Scholar 

  200. Thomsen, O. Ø, and J. A. Larsen, 1981. The effect of glucagon, dibutyrlic cyclic AMP and insulin on bile production in the intact rat and the perfused rat liver. Acta Physiol. Scand. 111: 23–30.

    PubMed  CAS  Google Scholar 

  201. Geist,R.E.,and R. S.Jones. 1971. Effect of selective and truncal vagotomy on insulin-stimulated bile secretion in dogs. Gastroenterology 60: 566–571.

    Google Scholar 

  202. Thomsen, O.Ø, and J. A. Larsen, 1983. Importance of perfusate hematocrit for insulin- and glucagon-induced choleresis in the perfused rat liver. Am. J. Physiol. 245: G59–G63.

    Google Scholar 

  203. Thomsen, O. Ø. 1983. Stimulatory effect of bile acids on insulin- induced choleresis in the rat. Am. J. Physiol. 244: G301–G307.

    PubMed  CAS  Google Scholar 

  204. Thomsen, O. Ø 1984. Mechanism and regulation of hepatic bile production. Scand. J. Gastroenterol. 19: (Suppl 97) 1–52.

    Google Scholar 

  205. Dyck, W. P., and H. D. Janowitz. 1971. Effect of glucagon on hepatic bile secretion in man. Gastroenterology 60: 400–404.

    PubMed  CAS  Google Scholar 

  206. Jones, R. S., R. E. Geist, and A. D. Hall. 1971. The choleretic effects of glucagon and secretin in the dog. Gastroenterology 60: 64–68.

    PubMed  CAS  Google Scholar 

  207. Morris, T. Q., G. F. Sardi, and S. E. Bradley. 1967. Character of glucagon-induced choleresis. Fed. Proc. 26: 774a.

    Google Scholar 

  208. Beaugie, J. M. 1972. Gastrointestinal hormones and bile flow. Ann. R. Coll. Surg. Engl. 50: 164–181.

    PubMed  CAS  Google Scholar 

  209. Pissidis, A. G., C. T. Bombeck, F. Merchant, and L. M. Nyhus. 1969. Hormonal regulation of bile secretion: A study in the isolated perfused liver. Surgery 66: 1075–1084.

    PubMed  CAS  Google Scholar 

  210. Forsmann, W. G., and S. Ito. 1977. Hepatocyte innervation in primates. J. Cell Biol. 74: 299–313.

    Google Scholar 

  211. Sutherland, S. D. 1965. The intrinsic innervation of the liver. Rev. Int. Hepatol. 15: 569–578.

    PubMed  CAS  Google Scholar 

  212. Nevasaari, K., and N. T. Kaerki. 1976. The effect of acetylcholine on bile flow. Arch. Int. Pharmacodyn. Ther. 221: 283–293.

    PubMed  CAS  Google Scholar 

  213. Fritz, M. E., and F. B. Brooks. 1963. Control of bile flow in the cholecystectomized dog. Am. J. Physiol. 204: 825–828.

    PubMed  CAS  Google Scholar 

  214. Baldwin, J., F. W. Heer, R. Albo, O. Paloso, L. Ruby, and W. Silen. 1966. Effect of vagus nerve stimulation on hepatic secretion of bile in human subjects. Am. J. Surg. 111: 66–69.

    PubMed  CAS  Google Scholar 

  215. Harty, R. F., R. C. Rose, and D. L. Nahrwald. 1974. Stimulation of hepatic bile secretion by dopamine. J. Surg. Res. 17: 359–363.

    PubMed  CAS  Google Scholar 

  216. Ho, K. J., and J. L. Drummond. 1975. Circadian rhythm of biliary excretion and its control mechanisms in rats with chronic biliary drainage. Am. J. Physiol. 229: 1427–1437.

    PubMed  CAS  Google Scholar 

  217. Ho, K. J. 1976. Circadian distribution of bile acids in the enterohepatic circulatory system in rats. Am. J. Physiol. 230: 1331–1335.

    PubMed  CAS  Google Scholar 

  218. Mitropoulos, K. A. 1975. Diurnal variations in bile acid metabolism. In: The Hepatobiliary System. W. Taylor, ed. Plenum Press, New York. pp. 409–427.

    Google Scholar 

  219. Hanzon, V. 1952. Liver cell secretion under normal and pathologic conditions studied by fluorescence microscopy on living rats. Acta Physiol. Scand. Suppl. 101 28: 1–268.

    Google Scholar 

  220. Gebhardt, R., and W. Jung. 1982. Primary cultures of rat hepatocytes as a model system of canalicular development, biliary secretion, and intrahepatic cholestasis. I. Distribution of filipin- cholesterol complexes during de novo formation of bile canaliculi. Eur. J. Cell Biol. 29: 68–76.

    PubMed  CAS  Google Scholar 

  221. Goresky, C. A. 1977. Hepatic membrane carrier transport pro¬cesses: Their involvement in bilirubin uptake. In: The Chemistry and Physiology of Bile Pigments. P. D. Berk and N. I. Berlin, eds. U.S. Government Printing Office, Washington, D.C. pp. 265–281.

    Google Scholar 

  222. Lee, K., and L. M. Gartner. 1978. Bilirubin binding by plasma proteins: A critical evaluation of methods and clinical implica¬tions. In: Reviews in Perinatal Medicine, Volume 2. E. M. Scarpelli and E. V. Cosmi, eds. Raven Press, New York. pp. 318–343.

    Google Scholar 

  223. Goodman, D. S. 1958. The interaction of human serum albumin with long-chain fatty acid anions. J. Am. Chem. Sco. 80: 3892–3898.

    CAS  Google Scholar 

  224. Baker, K. J., and S. E. Bradley. 1966. Binding of sulfobromophthalein (BSP) sodium by plasma albumin: Its role in hepatic BSP extraction. J. Clin. Invest. 45: 281–287.

    PubMed  CAS  Google Scholar 

  225. Goresky, C. A. 1964. Initial distribution and rate of uptake of sulfobromophthalein in the liver. Am. J. Physiol. 207: 13–26.

    PubMed  CAS  Google Scholar 

  226. Stremmel, W., N. Tavoloni, and P. D. Berk. 1983. Uptake of bilirubin by the liver. Semin. Liver Dis. 3: 1–10.

    Google Scholar 

  227. Weisiger, R., J. Gollan, and R. Ockner. 1981. Receptor for albumin on the liver cell surface may mediate uptake of fatty acids and other albumin-bound substances. Science 211: 1048 - 1051.

    PubMed  CAS  Google Scholar 

  228. Weisiger, R. A., J. L. Gollan, and R. K. Ockner. 1982. The role of albumin in hepatic uptake processes. Prog. Liver Dis. 7: 71–85.

    PubMed  CAS  Google Scholar 

  229. Weisiger, R. A., C. Zacks, N. Smith, and J. L. Boyer. 1984. Effect of albumin on extraction of sulfobromophthalein by perfused elasmobranch liver: Evidence for dissociation-limited uptake. Hepatology 4: 492–501.

    PubMed  CAS  Google Scholar 

  230. Goresky, C. A. 1965. The hepatic uptake and excretion of sul-fobromophthalein and bilirubin. Can. Med. Assoc. J. 92: 851–857.

    PubMed  CAS  Google Scholar 

  231. Hunton, D. B., J. L. Bollman, andH. N. Hoffman. 1961. II. The plasma removal of indocyanine green and sulfobromophthalein: Effect of dosage and blocking agents. J. Clin. Invest. 40: 1648–1655.

    PubMed  CAS  Google Scholar 

  232. Bloomer, J. R., and J. Zaccaria. 1976. Effect of graded loads on bilirubin transport by perfused rat liver. Am. J. Physiol. 230: 736–742.

    PubMed  CAS  Google Scholar 

  233. Scharschmidt, B. F., J. G. Waggoner, and P. D. Berk. 1975. Hepatic organic anion uptake in the rat. J. Clin. Invest. 56: 1280–1292.

    PubMed  CAS  Google Scholar 

  234. Paumgartner, G., and J. Reichen. 1976. Kinetics of hepatic uptake of unconjugated bilirubin. Clin. Sci. Mol. Med. 51: 169–176.

    PubMed  CAS  Google Scholar 

  235. Laperche, Y., A.-M. Preux, G. Feldmann, J.-L. Maha, and P. Berthelot. 1981. Effect of fasting on organic anion uptake by isolated rat liver cells. Hepatology 1: 617–621.

    PubMed  CAS  Google Scholar 

  236. Anwer, M. D., and D. Hegner. 1978. Effect of organic anions on bile acid uptake by isolated rat hepatocytes. Hoppe-Seylers Z. Physiol. Chem. 359: 1027–1030.

    PubMed  CAS  Google Scholar 

  237. Maha, J.-L., P. Duvaldestin, D. Dhumeaux, and P. Berthelot. 1977. Biliary transport of cholephilic dyes: Evidence for two different pathways. Am. J. Physiol. 232: E445–E450.

    Google Scholar 

  238. Schwarz, L. R., R. Gozt, and C. D. Klaassen. 1979. Uptake of sulfobromophthalein-glutathione conjugate by isolated hepatocytes. Am. J. Physiol 239: G118–G123.

    Google Scholar 

  239. von Dippe, P., P. Drain, and D. Levy. 1983. Synthesis and transport characteristics of photo affinity probes for the hepatocyte bile acid transport system. J. Biol. Chem. 258: 8890–8895.

    Google Scholar 

  240. Reichen, J., and P. D. Berk. 1979. Isolation of an organic anion binding protein from rat liver plasma membrane fractions by affinity chromatography. Biochem. Biophys. Res. Commun. 91: 484–489.

    PubMed  CAS  Google Scholar 

  241. Wolkoff, A. W., andC. T. Chung. 1980. Identification, purification and partial characterization of an organic anion binding protein from rat liver cell plasma membrane. J. Clin. Invest. 65: 1152–1161.

    PubMed  CAS  Google Scholar 

  242. Stremmel, W., M. Gerber, V. Glezerov, S. N. Thung, S. Koch- wa, and P. D. Berk. 1982. Physicochemical and immunohistological studies of a sulfobromophthalein- and bilirubin- binding protein from rat liver plasma membranes. Hepatology 2: 717a.

    Google Scholar 

  243. Tiribelli, C., G. Lunazzi, G. L. Luciana, E. Panfivi, B. Gazzin, G. Liut, G. Sandri, and G. Sottocasa. 1978. Isolation of a sulfobromophthalein-binding protein from hepatocyte plasma membrane. Biochim. Biophys. Acta 532: 105–112.

    PubMed  CAS  Google Scholar 

  244. Stremmel, W., G. Strohmeyer, F. Borchard, S. Kochwa, and P. D. Berk. 1983. Isolation and partial characterization of a fatty acid binding protein from rat liver plasma membranes. Hepatology 3: 823a.

    Google Scholar 

  245. Kramer, W., U. Bickel, H.-P. Buscher, W. Gerok, and G. Kurz. 1980. Binding proteins for bile acids in membranes of hepatocytes revealed by photo affinity labelling. Hoppe-Seylers Z. Physiol. Chem. 361: 1307a.

    Google Scholar 

  246. Levy, D., and P. von Dippe. 1983. Reconstitution of the bile acid transport system derived from hepatocyte sinusoidal membranes. Hepatology 3: 837a.

    Google Scholar 

  247. Berk, P. D., T. F. Blaschke, and J. G. Waggoner. 1972. Defective BSP clearance in patients with constitutional hepatic dysfunction (Gilbert’s syndrome). Gastroenterology 63: 472–481.

    PubMed  CAS  Google Scholar 

  248. Martin, J. F., J. M. Vierling, A. W. Wolkoff, B. F. Scharschmidt, J. Vergalla, J. G. Waggoner, and P. D. Berk. 1976. Abnormal hepatic transport of indocyanine green in Gilbert’s syndrome. Gastroenterology 70: 385–391.

    PubMed  CAS  Google Scholar 

  249. Nambu, M., T. Namihisa, T. Yamashiro, H. Ohama, M. Maeda, and H. Ueda. 1980. Plasma disappearance of serum bile acids in patients with constitutional hyperbilirubinemia and constitutional ICG excretory defect. Jpn. J. Gastroenterol 77: 1369–1377.

    CAS  Google Scholar 

  250. Ohkubo, H., K. Okuda, and S. Iida. 1981. A constitutional unconjugated hyperbilirubinemia combined with indocyanine green intolerance: A new functional disorder? Hepatology 1: 319–324.

    PubMed  CAS  Google Scholar 

  251. Ketterer, B., B. Neumcke, and P. Lauger. 1971. Transport mechanism of hydrophobic ions through lipid bilayer membranes. J. Membr. Biol 5: 225–245.

    CAS  Google Scholar 

  252. Benz, R., P. Lauger, and K. Janko. 1976. Transport kinetics of hydrophobic ions in lipid bilayer membranes: Charge-pulse relaxation studies. Biochim. Biophys. Acta 455: 701–720.

    PubMed  CAS  Google Scholar 

  253. Levi, A. J., Z. Gatmaitan, and I. M. Arias. 1969. Two hepatic cytoplasmic protein fractions, Y and Z and their possible role in hepatic uptake of bilirubin, sulphobromphthalein, and other anions. J. Clin. Invest. 48: 2156–2167.

    PubMed  CAS  Google Scholar 

  254. Littwack, G., B. Ketterer, and I. M. Arias. 1971. Ligandin, a hepatic protein which binds steroids, bilirubin, carcinogens and a number of exogenous organic anions. Nature (London) 234: 466–467.

    Google Scholar 

  255. Listowsky, I., Z. Gaitmaitan, and I. M. Arias. 1978. Ligandin retains and albumin loses bilirubin binding capacity in liver cytosol. Proc. Natl Acad. Sci. USA 75: 1213–1216.

    PubMed  CAS  Google Scholar 

  256. Hales, B. F., and A. H. Neims. 1976. Developmental aspects of glutathione S-transferase B (ligandin) in rat liver. Biochem. J. 160: 231–236.

    PubMed  CAS  Google Scholar 

  257. Levi, A. J., Z. Gaitmaitan, and I. M. Arias. 1970. Deficiency of hepatic organic anion binding protein, impaired organic anion uptake by liver and “physiologic” jaundice in newborn monkeys. N. Engl J. Med. 283: 1136–1139.

    PubMed  CAS  Google Scholar 

  258. Fleischner, G., J. Robbins, and I. M. Arias. 1972. Immunological studies of Y protein: A major cytoplasmic organic anion-binding protein in rat liver. J. Clin. Invest. 51: 677–684.

    PubMed  CAS  Google Scholar 

  259. Reyes, A., A. J. Levi, Z. Gaitmaitan, and I. M. Arias. 1971. Studies of Y & Z, two hepatic cytoplasmic organic anion-binding proteins: Effect of drugs, chemicals, hormones, and cholestasis. J. Clin. Invest. 50: 2242–2252.

    PubMed  CAS  Google Scholar 

  260. Kamisaka, K., I. Kistowsky, Z. Gaitmaitan, and I. M. Arias. 1975. Interactions of bilirubin and other ligands with ligandin. Biochemistry 14: 2175–2180.

    PubMed  CAS  Google Scholar 

  261. Boyer, J. L., J. Schwarz, and N. Smith. 1976. Biliary secretion in elasmobranchs. II. Hepatic uptake and biliary excretion of organic anions. Am. J. Physiol 230: 974–981.

    PubMed  CAS  Google Scholar 

  262. Wolkoff, A. W., C. A. Goresky, J. Sellin, Z. Gaitmaitan, and I. M. Arias. 1979. Role of ligandin in transfer of bilirubin from plasma into liver. Am. J. Physiol 236: E638–E648.

    PubMed  CAS  Google Scholar 

  263. Sugiyama, Y., T. Yamada, and N. Kaplowitz. 1982. Newly identified organic anion-binding proteins in rat cytosol. Biochim. Biophys. Acta 709: 342–352.

    PubMed  CAS  Google Scholar 

  264. Redick, J. A., W. B. Jakoby, and J. Baron. 1982. Immunohistochemical localization of glutathione S-transferases in livers of untreated rats. J. Biol. Chem. 257: 15200–15203.

    PubMed  CAS  Google Scholar 

  265. Vessey, D. A., J. Whitney, and J. L. Gollan. 1983. The role of conjugation reaction in enhancing biliary excretion of bile acids. Biochem. J. 214: 923–927.

    PubMed  CAS  Google Scholar 

  266. Gollan, J., and R. Schmid. 1982. Bilirubin update: Formation, transport and metabolism. Prog. Liver Dis. 8: 261–283.

    Google Scholar 

  267. Whelan, G., J. Hoch, and B. Combes. 1970. A direct assessment of the importance of conjugation for biliary transport of sul- fobromphthalein sodium. J. Lab. Clin. Med. 75: 542–557.

    PubMed  CAS  Google Scholar 

  268. Wolkoff, A. W. 1983. Bilirubin metabolism and hyperbilirubinemia. Semin. Liver Dis. 3: 1–83.

    Google Scholar 

  269. Gutstein, S., S. Alpert, and I. M. Arias. 1968. Studies of hepatic excretory function. IV. Biliary excretion of sulfobromophthalein sodium in a patient with the Dubin-Johnson syndrome and a biliary fistula. Isr. J. Med. Sci. 4: 36–40.

    PubMed  CAS  Google Scholar 

  270. Alpert, S., M. Mosher, A. Shanske, and I. M. Arias. 1969. Multiplicity of hepatic excretory mechanisms for organic anions. J. Gen. Physiol 53: 238–247.

    PubMed  CAS  Google Scholar 

  271. Cornelius, C. E. 1969. Organic anion transport in mutant sheep with congenital hyperbilirubinemia. Arch. Environ. Health 19: 852–856.

    PubMed  CAS  Google Scholar 

  272. Clarenberg, R., and C.-C. Kao. 1973. Shared and separate pathways for biliary excretion of bilirubin and BSP in rats. Am. J. Physiol 225: 192–200.

    Google Scholar 

  273. Boyer, J. L., R. L. Scheig, and G. Klatskin. 1970. The effect of sodium taurocholate on the hepatic metabolism of sul-fobromophthalein sodium (BSP): The role of bile flow. J. Clin. Invest. 49: 206–215.

    PubMed  CAS  Google Scholar 

  274. Vonk, R. J., M. Danhof, T. Coenraads, A. B. D. van Doom, K. Keulemans, A.H.J. Scaf, and D. K. F. Meijer. 1979. Influence of bile salts on hepatic transport of dibromosulphthalein. Am. J. Physiol 237: E524–E534.

    PubMed  CAS  Google Scholar 

  275. Loeb, P. M., J. L. Barnhart, and R. N. Berk. 1978. The dependence of biliary excretion of iopanoic acid on bile salts. Gastroenterology 74: 174–181.

    PubMed  CAS  Google Scholar 

  276. Vonk, R. J., A. B. D. van Doom, A. H. J. Scaf, and D. K. F. Meijer. 1977. Choleresis and hepatic transport mechanisms. III. Binding of ouabain and K-strophanthoiside to biliary micelles and influence of choleresis on their biliary excretion. Naunyn- Schmiedebergs Arch. Pharmacol 300: 173–177.

    CAS  Google Scholar 

  277. Delage, Y., M. Dumont, and S. Erlinger. 1976. Effect of glycodihydrofusidate on sulfobromophthalein transport maximum in the hamster. Am. J. Physiol 231: 1875–1878.

    PubMed  CAS  Google Scholar 

  278. Schanker, L. S., and H. M. Solomon. 1963. Active transport of quaternary ammonium compounds in bile. Am. J. Physiol 204: 829–832.

    PubMed  CAS  Google Scholar 

  279. Schanker, L. S. 1968. Secretion of organic compounds in bile. In: Handbook of Physiology, Section 6. C. F. Code, ed. American Physiological Society, Washington, D. C. pp. 2433–2449.

    Google Scholar 

  280. Russell, J. Q., and C. D. Klaassen. 1972. Species variation in the biliary excretion of ouabain. J. Pharmacol Exp. Ther. 103: 513–519.

    Google Scholar 

  281. Meijer, D. K. F., R. J. Vonk, E. J. Scholtens, and W. G. Levine. 1976. The influence of dehydrocholate on hepatic uptake and excretion of 3H-taurocholate and 3H-ouabain. Drug Metab. Dispos. 4: 1–7.

    PubMed  CAS  Google Scholar 

  282. Erttmann, R. R., and K. H. Damm. 1975. Influence of bile flow, theophylline and some organic anions on the biliary excretion of 3H-ouabain in rats. Arch. Int. Pharmacodyn. Ther. 218: 290–298.

    PubMed  CAS  Google Scholar 

  283. Balint, J. A., E. C. Kyriakides, H. L. Spitzer, and E. S. Morrison. 1965. Lecithin fatty acid composition in bile and plasma of man, dogs, rats, and oxen. J. Lipid Res. 6: 96–99.

    PubMed  CAS  Google Scholar 

  284. Coleman, R., S. Iqbal, P. P. Godfrey, and D. Billington. 1979. Membranes and bile formation. Biochem. J. 178: 201–208.

    PubMed  CAS  Google Scholar 

  285. Mazer, N. A., and M. C. Carey. 1980. Quasielastic light scattering studies of aqueous biliary lipid systems: Cholesterol solubilization and precipitation in model bile solutions. Biochemistry 19: 601–615.

    PubMed  CAS  Google Scholar 

  286. Reuben, A., K. E. Howell, and J. L. Boyer. 1982. Effects of taurocholate on the size of mixed lipid micelles and their associations with pigment and proteins in rat bile. J. Lipid Res. 23: 1039–1052.

    PubMed  CAS  Google Scholar 

  287. Turley, S. D., and J. M. Dietschy. 1979. Regulation of biliary cholesterol output in the rat: Dissociation from the rate of hepatic cholesterol synthesis, the size of the hepatic cholesteryl ester pool, and the hepatic uptake of chylomicron cholesterol. J. Lipid Res. 20: 923–934.

    PubMed  CAS  Google Scholar 

  288. Schwartz, C. C., M. Berman, Z. R. Vlahcevic, L. G. Halloran, D. H. Gregory, and L. Swell. 1978. Multicompartmental analysis of cholesterol metabolism in man: Characterization of the hepatic bile acid and biliary cholesterol precursor sites. J. Clin. Invest. 61: 408–423.

    PubMed  CAS  Google Scholar 

  289. Gregory, D. H., Z. R. Vlahcevic, P. Schatzki, and L. Swell. 1975. Mechanism of secretion of biliary lipids. I. Role of bile canalicular and microsomal membranes in the synthesis and transport of biliary lecithin and cholesterol. J. Clin. Invest. 55: 105–114.

    PubMed  CAS  Google Scholar 

  290. Robins, S. J., and H. Brunengraber. 1982. Origin of biliary cholesterol and lecithin in the rat: Contribution of new synthesis and preformed hepatic stores. J. Lipid Res. 23: 604–608.

    PubMed  CAS  Google Scholar 

  291. Small, D. M. 1970. The formation of gallstones. Adv. Inter. Med. 16: 243–264.

    CAS  Google Scholar 

  292. Gregory, D. H., Z. R. Vlahcevic, P. Schatzki, and L. Swell. 1975. Mechanism of secretion of biliary lipid. I. Role of bile canalicular and microsomal membranes in the synthesis and transport of biliary lecithin and cholesterol. J. Clin. Invest. 55: 105–114.

    PubMed  CAS  Google Scholar 

  293. Lafont, H., D. Lairon, N. Domingo, G. Nalbone, and J. C. Hauton. 1974. Does a lecithin-polypeptide association in bile originate from membrane structural subunits? Biochimie 56: 465–468.

    PubMed  CAS  Google Scholar 

  294. Sewell, R. B., S. J. T. Mao, T. Kawamoto, and N. F. LaRusso. 1983. Apolipoproteins of high, low, and very low density lipoproteins in human bile. J. Lipid Res. 24: 391–401.

    PubMed  CAS  Google Scholar 

  295. Turley, S. D., and J. M. Dietschy. 1982. Cholesterol metabolism and excretion. In: The Liver: Biology and Pathobiology. I. Arias, H. Popper, D. Schacter, and D. A. Shafritz, eds. Raven Press, New York. pp. 467–492.

    Google Scholar 

  296. Montet, J. C., A. M. Montet, A. Gerolami, and J. C. Hauton. 1975. Effect of 3-acetoxy fusidate on the biliary secretion of lipids in the rat. Biol. Gastroenterol. 8: 53–62.

    CAS  Google Scholar 

  297. Hardison, W. G. M., and J. T. Apter. 1972. Micellar theory of biliary cholesterol excretion. Am. J. Physiol. 222: 61–67.

    PubMed  CAS  Google Scholar 

  298. Soloway, R. D., A. F. Hofmann, P. J. Thomas, L. J. Schoenfield, and P. D. Klein. 1973. Triketocholanic (dehydrocholic) acid: Hepatic metabolism and effect on bile flow and biliary lipid secretion in man. J. Clin. Invest. 52: 715–724.

    PubMed  CAS  Google Scholar 

  299. Apstein, M. D., and S.J. Robbins. 1982. Effect of organic anions on biliary lipids in the rat. Gastroenterology 83: 1120–1126.

    PubMed  CAS  Google Scholar 

  300. Schaffer, E. A., and R. M. Preshaw. 1981. Effects of sul- fobromophthalein excretion on biliary lipid secretion in humans and dogs. Am. J. Physiol. 240. G85–G89.

    Google Scholar 

  301. Apstein, M. D., and A. R. Russo. 1982. Where does bilirubin inhibit biliary phospholipid and cholesterol secretion? Hepatology 2: 143a.

    Google Scholar 

  302. Redinger, R. N., and D. M. Small. 1973. Primate biliary physiology. VIII. The effect of phenobarbital upon bile salt synthesis and pool size, biliary lipid secretion and bile composition. J. Clin. Invest. 52: 161–172.

    PubMed  CAS  Google Scholar 

  303. Strasberg, S. M., R. N. Redinger, D. M. Small, and R. H. Egdahl. 1982. The effect of elevated biliary tract pressure on biliary lipid metabolism and bile flow in nonhuman primates. J. Lab. Clin. Med. 99: 342–353.

    PubMed  CAS  Google Scholar 

  304. Dive, C. H., and J. F. Heremans. 1974. Nature and origin of the proteins in bile. I. Eur. J. Clin. Invest. 4: 235–239.

    PubMed  CAS  Google Scholar 

  305. Mullock, B. M., M. Dobrata, and R. H. Hinton. 1978. Sources of the proteins in rat liver. Biochim. Biophys. Acta 543: 497–507.

    PubMed  CAS  Google Scholar 

  306. Godfrey, P. P., M. J. Warner, and R. Coleman. 1981. Enzymes and proteins in bile. Biochem. J. 196: 11–16.

    PubMed  CAS  Google Scholar 

  307. Evans, W. H., T. Kremmer, and J. G. Culvenor. 1976. Role of membranes in bile formation: Comparison of the composition of bile and a liver bile canalicular plasma membrane fraction. Biochem. J. 154: 589–595.

    PubMed  CAS  Google Scholar 

  308. Kakis, G., and I. M. Yousef. 1978. Protein composition of rat bile. Can. J. Biochem. 56: 287–290.

    PubMed  CAS  Google Scholar 

  309. Mullock, B. M., R. H. Hinton, M. Dobrota, J. Peppard, and E. Orlans. 1980. Distribution of secretory component in hepatocytes and its mode of transfer into bile. Biochem. J. 190: 819–826.

    PubMed  CAS  Google Scholar 

  310. Hinton, R. H., M. Dobrota, and B. M. Mullock. 1980. Haptoglobin-mediated transfer of haemoglobin from serum into bile. FEBS Lett. 112: 247–250.

    PubMed  CAS  Google Scholar 

  311. Jones, A. L., R. H. Renston, and S. J. Burwen. 1982. Uptake and intracellular disposition of plasma-derived proteins and apoproteins by hepatocytes. Prog. Liver Dis. 8: 51–69.

    Google Scholar 

  312. Barnwell, S. G., P. P. Godfrey, P. J. Lowe, and R. Coleman. 1983. Biliary protein output by isolated perfused rat livers. Biochem. J. 210: 549–557.

    PubMed  CAS  Google Scholar 

  313. Thomas, P., C. A. Toth, and N. Zamcheck. 1982. The mechanism of biliary excretion of a!-acid glycoprotein in the rat: Evidence for a molecular weight-dependent, nonreceptor-mediated pathway. Hepatology 2: 800–803.

    PubMed  CAS  Google Scholar 

  314. Sternlieb, I. 1972. Functional implications of human portal and bile ductular ultrastructure. Gastroenterology 63: 321–327.

    PubMed  CAS  Google Scholar 

  315. Hardwicke, J., J. G. Rankin, K. J. Baker, and R. Preisig. 1964. The loss of protein in human and canine hepatic bile. Clin. Sci. 26: 509–517.

    PubMed  CAS  Google Scholar 

  316. Dive, C. H., R. A. Nadalini, J. P. Vaerman, and J. F. Heremans. 1974. Origin and nature of the proteins in bile. II. A comparative analysis of serum, hepatic lymph and bile proteins in the dog. Eur. J. Clin. Invest. 4: 241–246.

    PubMed  CAS  Google Scholar 

  317. Nagura, H., P. D. Smith, P. K. Nakane, and W. R. Brown. 1981. IgA in human bile and liver. J. Immunol. 126: 587–595.

    PubMed  CAS  Google Scholar 

  318. Renston, R. H., D. G. Maloney, A. L. Jones, G. T. Hradek, K. Y. Wong, and I. D. Goldfine. 1980. Bile secretory apparatus: Evidence for a vesicular transport mechanism for proteins in the rat, using horseradish peroxidase and 125I-insulin. Gastroenterology 78: 1373–1388.

    PubMed  CAS  Google Scholar 

  319. Lee, S. P., T. H. Lim, and A. J. Scott. 1979. Carbohydrate moieties of glycoproteins in human hepatic and gallbladder bile, gallbladder mucosa and gallstones. Clin. Sci. Mol. Med. 56: 533–538.

    CAS  Google Scholar 

  320. LaMont, J. T., A. S. Ventola, B. W. Trotman, and R. D. Soloway. 1983. Mucin content of human pigment gallstones. Hepatology 3: 377–382.

    PubMed  CAS  Google Scholar 

  321. Folsch, U. R., and K. G. Wormsley. 1977. The amino acid composition of rat bile. Experientia 33: 1055–1056.

    PubMed  CAS  Google Scholar 

  322. Fisher, M. M., and M. Kerly. 1964. Amino acid metabolism in the perfused rat liver. J. Physiol. (London) 174: 273–294.

    CAS  Google Scholar 

  323. Bartoli, G., and H. Sies. 1978. Reduced and oxidized glutathione efflux from liver. FEBS Lett. 86: 89–91.

    PubMed  CAS  Google Scholar 

  324. Bartoli, G. M., D. Haeberle, and H. Sies. 1978. Glutathione efflux from perfused rat liver and the relation to glutatione uptake by the kidney. In: Functions of Glutathione in Liver and Kidney. H. Sies and A. Wendel, eds. Springer-Verlag, Berlin, pp. 27–31.

    Google Scholar 

  325. Eberle, D., R. Clarke, and N. Kaplowitz. 1981. Rapid oxidation in vitro of endogenous and exogenous glutathione in bile of rats. J. Biol. Chem. 256: 2115–2117.

    PubMed  CAS  Google Scholar 

  326. Kaplowitz, N., D. E. Eberle, J. Petrini, J. Touloukian, M. C. Corvasce, and J. Kuhlenkamp. 1983. Factors influencing the efflux of hepatic glutathione into bile in rats. J. Pharmacol. Exp. Ther. 244: 141–147.

    Google Scholar 

  327. Prasad, A. S. 1976. Trace Elements in Human Health and Disease. eds. Academic Press, New York.

    Google Scholar 

  328. Klaassen, C. D. 1975. Biliary excretion of xenobiotics. CRC Crit. Rev. Toxicol. 4: 1–30.

    PubMed  CAS  Google Scholar 

  329. Klaassen, C. D. 1976. Biliary excretion of metals. Drug Metab. Rev. 5: 165–196.

    PubMed  CAS  Google Scholar 

  330. Frommer, D. 1974. Defective biliary excretion of copper in Wilson’s disease. Gut 15: 125.

    PubMed  CAS  Google Scholar 

  331. Ballatori, N., and T. W. Clarkson. 1983. Biliary transport of glutathione and methylmercury. Am. J. Physiol. 144: G435–G441.

    Google Scholar 

  332. Grasbeck, R., W. Nyberg, and P. Reizenstein. 1958. Biliary and fecal vit B12 excretion in man: An isotope study. Proc. Soc. Exp. Biol. Med. 97: 780–784.

    PubMed  CAS  Google Scholar 

  333. Green, R., D. W. Jacobsen, S. V. VanTonder, M. C. Kew, and J. Metz. 1981. Enterohepatic circulation of cobalamin in the non- human primate. Gastroenterology 81: 773–776.

    PubMed  CAS  Google Scholar 

  334. Kumar, R., S. Nagubandi, V. R. Mattox, and J. M. Londowski. 1980. Enterohepatic physiology of 1,25-dihydroxyvitamin D3. J. Clin. Invest. 65: 277–284.

    PubMed  CAS  Google Scholar 

  335. Aldercreutz, H., and T. Luukainen. 1967. Biochemical and clinical aspects of the enterohepatic circulation of estrogens. Acta Endocrinol. Copenhagen Suppl. 124: 101–140.

    Google Scholar 

  336. Laatikainen, T. 1970. Excretion of neutral steroid hormones in human bile. Ann. Clin. Res. 2 (Suppl. 5): 1–28.

    PubMed  Google Scholar 

  337. Taylor, W. 1971. The excretion of steroid hormone metabolites in bile and feces. Vitam. Horm. (N.Y.) 29: 201–285.

    Google Scholar 

  338. Avner, D. L., and M. M. Berenson. 1982. Effect of choleretics on canalicular transport of protoporphyrin in the rat liver. Am. J. Physiol. 242: G347–G353.

    PubMed  CAS  Google Scholar 

  339. Plaa, G. L., and B. G. Priestly. 1976. Intrahepatic cholestasis induced by drugs and chemicals. Pharmacol. Rev. 28: 207–273.

    PubMed  CAS  Google Scholar 

  340. Chenderovitch, J., S. Troupel, H. Renault, and J. Caroli. 1961. Le transfert du Na24 et du K52 du sang dans la bile chez le cobaye au cours de la cholérèse a débit bloqué (“stop-flow analysis”). Rev. Fr. Etud. Clin. Biol. 6: 584–589.

    PubMed  CAS  Google Scholar 

  341. Levine, R. A., and R. C. Hall. 1976. cAMP in secretin choleresis: Evidence for regulatory role in man and baboons but not in dogs. Gastroenterology 70: 537–544.

    Google Scholar 

  342. Rene, E., R. G. Danzinger, A. F. Hofmann, and M. Nakagaki. 1983. Pharmacologic effect of somatostatin on bile formation in the dog: Enhanced ductular reabsorption on the major mechanism of anticholeresis. Gastroenterology 84: 120–129.

    PubMed  CAS  Google Scholar 

  343. Lewis, M. H., A. L. Baker, and A. R. Moossa. 1982. Effect of somatostatin on determinants of bile flow in unanesthetized dogs. Ann. Surg. 195: 97–103.

    PubMed  CAS  Google Scholar 

  344. Ricci, G. L., and J. Fevery. 1981. Cholestatic action of somatostatin in the rat: Effect on the different fractions of bile secretion. Gastroenterology 81: 555–562.

    Google Scholar 

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  1. Liver Study Unit, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, 06510, USA

    James L. Boyer

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    Thomas E. Andreoli M.D.  & Stanley G. Schultz M.D.  & 

  2. Yale University School of Medicine, New Haven, Connecticut, USA

    Joseph F. Hoffman Ph.D.

  3. University of California, San Diego La Jolla, California, USA

    Darrell D. Fanestil M.D.

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Boyer, J.L. (1986). Mechanisms of Bile Secretion and Hepatic Transport. In: Andreoli, T.E., Hoffman, J.F., Fanestil, D.D., Schultz, S.G. (eds) Physiology of Membrane Disorders. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2097-5_35

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