Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 311, Issue 3, pp 273–284 | Cite as

Transfer across mucosal epithelium, tissue content and metabolic fate of125I-(ipodate-sodium) on isolated everted segments of rat small intestine

  • B. Komp
  • W. Forth
Article

Summary

  1. 1.

    Transfer and tissue content of125I-radioactivity was measured after administration of125I-(ipodate-sodium) to everted rat jejunal segments.

     
  2. 2.

    After having administered 10−5M125I-(ipodatesodium) on both sides of the everted sacs the S/M ratio of the concentration of125I-radioactivity was 1.5 in jejunal segments and 2.3 in ileal segments. The tissue content was nearly equal for both segments. According to the apparent partition coefficient for ipodate-sodium at pH7, the125I-radioactivity is accumulated in the tissue about 10-fold.

     
  3. 3.

    Lowering of the temperature of the incubation medium from 37°C to 15°C prevents the building up of a concentration gradient between the serosal and the mucosal side on either jejunal and ileal segments whereas the tissue content of125I-radioactivity was nearly unchanged.

     
  4. 4.

    With increasing concentrations (1.6·10−6–9.6·10−4 M) of125I-(ipodate-sodium) administered on the mucosal side the transfer and the tissue content of125I-radioactivity were decreased. This appears to be a toxic effect since in jejunal segments also the S/M ratio for the concentration of glucose decreases.

     
  5. 5.

    The analysis of the125I-radioactivity in the serosal fluid of jejunal segments showed that the bulk of the125I-radioactivity was present in the aqueous phase and only 33% as the unchanged ipodate-sodium in the organic phase. 10% of the125I-radioactivity must be attributed to inorganic iodine. The concentration of125I-(ipodate-sodium) administered in the mucosal fluid only was 3.2·10−6 M. At lower temperature (7°C) the bulk of the125I-radioactivity in the serosal fluid was found in the organic phase, i.e. as unchanged ipodate-sodium.

     
  6. 6.

    After the incubation of the aqueous phase with β-glucuronidase or NaOH about 97% of the125I-radioactivity could be extracted into the organic phase. This means that the bulk of the125I-radioactivity in the aqueous phase is present as a conjugate, e.g. ester glucuronide of the unchanged ipodate.

     
  7. 7.

    Apparently, the process of the conjugation of ipodate-sodium in the mucosal cells is involved in the transfer of the125I-radioactivity across the mucosal epithelium.

     

Key words

125I-(ipodate-sodium) Glucuronidation in the mucosal epithelium Transfer across mucosal epithelium Tissue content Metabolic conversion of ipodate-sodium during absorption 

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References

  1. Barker, W. M., Thompson, D. J., Ware, J. H.: Studies on the metabolism of 2,3,5-triiodobenzoic acid (TIBA). Fed. Proc. Fed. Am. Soc. Exp. Biol.26, 568 (1967)Google Scholar
  2. Diamond, J. M.: Standing gradient model of fluid transport in epithelia. Fed. Proc. Fed. Am. Soc. Exp. Biol.30, 6–13 (1971)Google Scholar
  3. Fisher, R. B., Parsons, D. S.: A preparation of surviving rat small intestine for the study of absorption. J. Physiol. (Lond.)110, 26–46 (1949)Google Scholar
  4. Forth, W.: Resorption von Eisen und chemisch verwandten Metallen in vitro und in vivo; die Spezifität eines eisenbindenden Systems in der Mucosa des Jejunums von Ratten. In: Frontiers of nuclear medicine (W. Horst, Hrsg.), p. 83. Berlin, Heidelberg, New York: Springer 1971Google Scholar
  5. Forth, W., Rummel, W.: Activation and inhibition of intestinal absorption by drugs. In: IEPT, Sect. 39b. Pharmacology of intestinal absorption: gastrointestinal absorption of drugs (Forth, W., Rummel, W., eds.), p. 171. Oxford: Pergamon Press 1975Google Scholar
  6. Gutenmann, W. H., Bache, C. A., Lisk, D. J.: Fate of the plant regulator 2,3,5-triiodobenzoic acid (TIBA) in the bovine. J. Agric. Food Chem.15, 600–604 (1967)Google Scholar
  7. Hartiala, K.: Metabolism of hormones, drugs and other substances by the gut. Physiol. Rev.53, 496–534 (1973)Google Scholar
  8. Harwart, A., Kimbel, K. H., Langecker, H., Willenbrink, J.: β-(3-Dimethylamino-methylenamino-2,4,6-trijodphenyl)-propionsäure als Gallekontrastmittel. Naunyn-Schmiedeberg's Arch. Exp. Path. Pharmak.237, 186–193 (1959)Google Scholar
  9. Josting, D., Winne, D., Bock, K. W.: Glucuronidation of paracetamol, morphine and 1-naphthol in the rat intestinal loop. Biochem. Pharmacol.25, 613–616 (1976)Google Scholar
  10. Knoefel, P. K.: Binding of iodinated radiocontrast agents to the plasma proteins. In: Radiocontrast agents; IEPT, Sect. 76, Vol. I and II (P. K. Knoefel, ed.), pp. 133–145. Oxford: Pergamon Press 1971Google Scholar
  11. Komp, B.: Intestinal absorption of125J-sodium-ipodate in rats. Naunyn-Schmiedeberg's Arch. Pharmacol.293, R44 (1976)Google Scholar
  12. Komp, B.: Formation of glucuronides of125J-Na-Ipodate during the transfer across the isolated jejunal and ileal segments in vitro of rats. Naunyn-Schmiedeberg's Arch. Pharmacol.297, R2 (1977)Google Scholar
  13. Komp, B.: Intestinale Resorption und metabolische Veränderung während des Resorptionsvorganges von125J-(Ipodat-Na) im Jejunum der Ratte. Inaugural-Dissertation; Fachbereich Biochemie und Pharmazie, Johann Wolfgang Goethe-Universität, Frankfurt/Main 1978Google Scholar
  14. Langecker, H., Harwart, A., Kolb, K.-H., Kramer, M.: Diglycolsäure-di-(3-Carboxy-2,4,4-trijodanilid) (Joglycamid), ein Kontrastmittel für intravenöse Cholangiographie. Naunyn-Schmiedeberg's Arch. Exp. Path. Pharmak.247, 493–508, (1964)Google Scholar
  15. Lee, J. S.: Role of mesenteric lymphatic system in water absorption from rat intestine in vitro. Am. J. Physiol.204, 92–96 (1963)Google Scholar
  16. McChesney, E. W.: The biotransformation of iodinated radiocontrast agents. In: Radiocontrast agents, IEPT Sect. 76, Vol. I and II (P. K. Knoefel, ed.), pp. 147–163. Oxford: Pergamon Press 1971Google Scholar
  17. Moy, P., Ebert, A. G.: Studies on the metabolism of 2,3,5-triiodobenzoic acid. Fedn. Proc. Fedn. Am. Soc. Exp. Biol.26, 567 (1967)Google Scholar
  18. Mudge, G. H.: Uricosuric action of cholecystographic agents. N. Engl. J. Med.284, 929–993 (1971)Google Scholar
  19. Nell, G., Forth, W., Rummel, W., Wanitschke, R.: Pathway of sodium moving from blood to intestinal lumen under the influence of oxyphenisation and deoxycholate. Naunyn-Schmiedeberg's Arch. Pharmacol.293, 31–37 (1976)Google Scholar
  20. Pfleger, K.: Methods for the investigation in animals. In: Pharmacology of intestinal absorption: Gastrointestinal absorption of drugs; IEPT, Sect. 39B, Vol. 1a, 2 (W. Forth, W. Rummel, eds.), pp. 809–811, Oxford: Pergamon Press 1975Google Scholar
  21. Rosenstrauch, L. S.: Radiocontrast of the gall, bladder and the biliary ducts. In: Radiocontrast agents, IEPT, Sect. 76, Vol. I and II (P. K. Knoefel, ed.), pp. 237–260. Oxford: Pergamon Press 1971Google Scholar
  22. Rummel, W., Stupp, F. H.: Der Einfluß von Kalium und Calcium auf die Salz-, Glukose- und Wasserresorption des isolierten Dünndarmes. Naunyn-Schmiedeberg's Arch. Pharmakol. Exp. Pathol.240, 79–92 (1960)Google Scholar
  23. Schulze, D., Kaps, H. P.: Gerinnungshemmende Wirkungen trijodierter Röntgenkontrastmittel. Arzneim. Forsch. (Drug. Res.)27, 972–975 (1977)Google Scholar
  24. Smith, R. L.: Excretion of drugs in bile. In: Concepts in biochemical pharmacology. Part 1; Handbook of exper. pharmacol. XXVIII/1, (B. B. Broedie, J. R. Gilette, eds.), pp. 354–389. Berlin, Heidelberg, New York: Springer 1971Google Scholar
  25. Sperber, I., Sperber, G.: Hepatic excretion of radiocontrast agents. In: Radiocontrast agents, IEPT, Sect. 76, Vol. I and II (P. K. Knoefel, ed.), pp. 165–235. Oxford: Pergamon Press 1971Google Scholar
  26. Weiner, J. M.: Transport of weak acids and bases. In: Handbook of physiology, Sect. 8, renal physiology (I. Orloff, R. W. Berliner, S. R. Geiger, eds.), pp. 521–594. Washington, D. C.: American Physiological Soc. 1973Google Scholar
  27. Wilson, T. H., Wiseman, G.: The use of sacs of everted small intestine for the study transferrence of substance from the mucosal to the serosal surface. J. Physiol. (Lond.)123, 116–125 (1954)Google Scholar
  28. Wollenberg, P., Ullrich, V.: In vitro vasculary perfused small intestine of the mouse for the investigation of absorption and biotransformation of foreign compounds. Naunyn-Schmiedeberg's Arch. Pharmacol.307, R3 (1979)Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • B. Komp
    • 1
  • W. Forth
    • 1
  1. 1.Institut für Pharmakologie und Toxikologie der Ruhr-Universität BochumBochum 1Federal Republic of Germany

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