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Choleresis and hepatic transport mechanisms

II. Influence of bile salt choleresis and biliary micelle binding on biliary excretion on various organic anions

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Summary

To investigate, whether binding to micelles has a function in hepatic transport, biliary excretion of three organic anions, phenolphthalein-\-D-glucuronide (PG), dibromosulphthalein (DBSP) and indocyanine green (ICG) was studied in rats during saline, taurocholate or dehydrocholate administration. Taurocholate causes a weak choleresis with formation of biliary micelles, dehydrocholate a strong choleresis with little micelle formation. The two bile salts did not uniformly influence biliary excretion of the organic anions: biliary excretion of ICG (12.9 μmoles/kg) and DBSP (75.0 μmoles/kg) was stimulated by both bile salts: ICG excretion most pronounced by taurocholate and DBSP excretion most strongly by dehydrocholate. Biliary output of PG (25.8 and 200 μmoles/kg) was not stimulated by bile salt administration. Binding of PG, DBSP and ICG to biliary micelles was studied in sedimentation experiments by ultracentrifugation. PG, DBSP and ICG in bile showed a similar sedimentation pattern as 3H-taurocholate in bile, which indicates an association of all three anions with biliary micelles.

Thus, the influence of bile salts on biliary transport of organic anions varies with the compound studied and the bile salt used, effects which cannot be explained by differences in binding to biliary micelles.

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References

  • Barnhart, J. L., Combes, B.: Effect of theophylline on hepatic excretory function. Amer. J. Phys. 227, 194–199 (1974)

    Google Scholar 

  • Berk, R. N., Goldberger, L. E., Loeb, P. M.: The role of bile salts in the hepatic excretion of iopanoic acid. Invest. Rad. 9, 7–15 (1974)

    Google Scholar 

  • Bickel, M. H., Minder, R.: Metabolism and biliary excretion of the lipophilic drug molecules, imipramine and desmethylimipramine in the rat-II. Uptake into bile micelles. Biochem. Pharmacol. 19, 2437–2443 (1970)

    Google Scholar 

  • Billing, B. H., Jansen, F. H., Bilton, E.: The effect of bile depletion on the biliary excretion of unconjugated bilirubin and bilirubin conjugates. In: The liver. Quantitative aspects of structure and function, pp. 386–391, Eds.: G. Paumgartner and R. Preisig. Basel: Karger 1973

    Google Scholar 

  • Bloomer, J. R., Boyer, J. L., Klatskin, G.: Inhibition of bilirubin excretion in man during dehydrocholate choleresis. Gastroenterology 65, 929–935 (1973)

    Google Scholar 

  • Boyer, J. L., Scheig, R. L., Klatskin, G.: The effect of sodium taurocholate on the hepatic metabolism of sulfobromophtalein sodium (BSP). The role of bile flow. J. clin. Invest. 49, 206–215 (1970)

    Google Scholar 

  • Carey, M. C., Small, D. M.: Micelle formation by bile salts. Arch. intern. Med. 130, 506–527 (1972)

    Google Scholar 

  • Cherrick, G. R., Stein, S. W., Leevy, C. M., Davidson, C. S.: Indocyanine green: observations on its physical properties, plasma decay and hepatic extraction. J. clin. Invest. 39, 592–600 (1960)

    Google Scholar 

  • Cook, D. L., Lawler, C. A., Green, D. M.: Studies on the effect of hydrocholeretic agents on hepatic excretory mechanisms. J. Pharmacol. exp. Ther. 110, 293–299 (1954)

    Google Scholar 

  • Desai, J. C., Glover, J., Joo, C. N.: The form of dispersion of sterols in bile and plasma. In: The biliary system, pp. 145–164. Ed.: W. Taylor. Oxford: Blackwell Scientific Publications 1965

    Google Scholar 

  • Desjeux, J. F., Erlinger, S., Dumont, M.: Metabolism and influence on bile secretion in dog of dehydrocholate. Biol. Gastroenterol. (Paris) 6, 9–19 (1973)

    Google Scholar 

  • Dhumeaux, D., Berthelot, P., Preaux, A. M., Erlinger, S., Fauvert, R.: A critical study of the concept of maximal biliary transport of sulfobromophtalein in the Wistar rat. Rev. Europ. Etud. clin. Biol. 15, 279–286 (1970)

    Google Scholar 

  • Erlinger, S., Dumont, M.: Influence of theophylline on bile formation in the dog. Biomedicine 19, 27–32 (1973a)

    Google Scholar 

  • Erlinger, S., Dumont, M.: Influence of canalicular bile flow on BSP transport maximum in bile in the dog. In: The liver. Quantitative aspects of structure and function, pp. 306–314. Eds.: G. Paumgartner and R. Preisig. Basel: Karger 1973b

    Google Scholar 

  • Forker, E. L., Gibson, G. E.: Interaction between sulfobromophtalein (BSP) and taurocholate: The kinetics of transport from liver cells to bile in rats. In: The liver. Quantitative aspects of structure and function, pp. 326–336. Eds.: G. Paumgartner and R. Preisig, Basel: Karger 1973

    Google Scholar 

  • Gérolami, A., Crotte, C., Montet, J.-C., Vigne, J.-L., Granger, M., Mule, A.: Métabolisme de l'acide dehydrocholique. Etude chromatographique de ses dérevés dans la bile. Etude “in vitro” de leur capacité a former des micelles mixtes. Biol. Gastroenterol. (Paris) 5, 265–272 (1972)

    Google Scholar 

  • Gibson, G. E., Forker, E. L.: Canalicular bile flow and bromosulfophthalein transport maximum: The effect of a bile salt-independent choleretic, SC-2644. Gastroenterology 66, 1046–1053 (1974)

    Google Scholar 

  • Goresky, C. A., Haddad, H. H., Kluger, W. S., Nadeau, B. E., Bach, G. G.: The enhancement of maximal bilirubin excretion with taurocholate-induced increments in bile flow. Canad. J. Phys. Pharm. 52, 389–403 (1974)

    Google Scholar 

  • Gronwall, R., Cornelius, C. E.: Maximal biliary excretion of sulfobromophthalein in sheep. Amer. J. digest. Dis. 15, 37–48 (1970)

    Google Scholar 

  • Hardison, W. G.: Metabolism of sodium dehydrocholate by the rat liver; its effect on micelle formation in bile. J. Lab. clin. Med. 77, 811–820 (1971)

    Google Scholar 

  • Hardison, W. G. M., Apter, J. T.: Micellar theory of biliary cholesterol excretion. Amer. J. Phys. 222, 61–67 (1972)

    Google Scholar 

  • Hillier, A. P.: The effect of taurocholate on the biliary secretion of thyroxine in the rat liver. Endocrinology 94, 272–275 (1974)

    Google Scholar 

  • Horak, W., Grabner, G., Paumgartner, G.: Inhibition of bile salt-independent bile formation by indocyanine green. Gastroenterology 64, 1005–1012 (1973)

    Google Scholar 

  • Javitt, N. B.: Phenol 3,6 dibromphthalein disulfonate. A new compound for the study of liver disease. Proc. Soc. exp. Biol. (N. Y.) 117, 254–257 (1964)

    Google Scholar 

  • Klaassen, C. D., Plaa, G. L.: Plasma disappearance and biliary excretion of indocyanine green in rats, rabbits and dogs. Toxicol. appl. Pharmacol. 15, 374–384 (1969)

    Google Scholar 

  • Macarol, V., Morris, T. Q., Baker, K. J., Bradley, S. E.: Hydrocortisone choleresis in the dog. J. clin. Invest. 49, 1714–1723 (1970)

    Google Scholar 

  • Meijer, D. K. F., Wester, J., Gunnink, M.: Distribution of quaternary ammonium compounds between particulate and soluble constituents of rat liver in relation to their transport from plasma into bile. Naunyn-Schmiedeberg's Arch. Pharmacol. 273, 179–192 (1972)

    Google Scholar 

  • Millburn, P., Smith, R. L., Williams, R. T.: Biliary excretion of foreign compounds. Biochem. J. 105, 1275–1281 (1967)

    Google Scholar 

  • Morris, T. Q.: Choleretic responses to cyclic AMP and theophylline in the dog. Gastroenterology 62, 187 (abstract) (1972)

    Google Scholar 

  • Mulder, G. J.: The rate limiting step in the biliary elimination of some substrates of uridinediphosphate glucuronyltransferase in the rat. Biochem. Pharmacol. 22, 1751–1763 (1973)

    Google Scholar 

  • O'Maille, E. R. L., Richards, T. G., Short, A. H.: Factors determining the maximal rate of organic anion secretion by the liver and further evidence of the hepatic site of action of the hormone secretin. J. Physiol. (Lond.) 186, 424–438 (1966)

    Google Scholar 

  • Ritt, D. J., Combes, B.: Enhancement of apparent excretory maximum of BSP by taurocholate and dehydrocholate. J. clin. Invest. 46, 1108–1109 (1967)

    Google Scholar 

  • Schulze, P. J., Czok, G.: Studies on the decrease in bile flow produced by sulfobromophthalein. Toxicol. appl. Pharmacol. 28, 406–417 (1974)

    Google Scholar 

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

    Google Scholar 

  • Sperber, I.: Billary secretion of organic anions and its influence on bile flow. The biliary system, pp. 457–467. Ed.: W. Taylor. Oxford: Blackwell Scientific Publications 1965

    Google Scholar 

  • Swell, L., Entenman, C., Leong, G. F., Holloway, R. J.: Bile acids and lipid metabolism IV. Influence of bile acids on biliary and liver organelle phospho-lipids and cholesterol. Amer. J. Phys. 215, 1390–1396 (1968)

    Google Scholar 

  • Varga, F., Fischer, E., Szily, T. S.: Biliary excretion of bromsulphtalein and glutathione conjugate of bromsulphtalein in rats pretreated with diethyl maleate. Biochem. Pharmacol. 23, 2617–2623 (1974)

    Google Scholar 

  • Vonk, R. J., v. d. Veen, H., Prop, G., Meijer, D. K. F.: The influence of taurocholate and dehydrocholate choleresis on plasma disappearance and biliary excretion of indocyanine green in the rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 282, 401–410 (1974)

    Google Scholar 

  • Wheeler, H. O., King, K. K.: Biliary excretion of lecithin and cholesterol in the dog. J. clin. Invest. 51, 1337–1350 (1972)

    Google Scholar 

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Authors and Affiliations

  1. Dept. Pharmacol., State University of Groningen, Bloemsingel 1, Groningen, The Netherlands

    R. J. Vonk, P. Jekel & D. K. F. Meijer

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  1. R. J. Vonk
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  2. P. Jekel
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  3. D. K. F. Meijer
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The previously published paper of Vonk et al. (1974) is regarded as paper I in this series.

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Vonk, R.J., Jekel, P. & Meijer, D.K.F. Choleresis and hepatic transport mechanisms. Naunyn-Schmiedeberg's Arch. Pharmacol. 290, 375–387 (1975). https://doi.org/10.1007/BF00499950

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  • DOI: https://doi.org/10.1007/BF00499950

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