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Comparative studies on the uptake of 14C-bile acids and 3H-demethylphalloin in isolated rat liver cells

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Abstract

The inward transport of bile acids in isolated hepatocytes competes with the uptake of phallotoxins. Cholate, taurocholate and glycocholate added 30 s prior to phallotoxins reduce their uptake in a concentration dependent manner. 100 μM bile acids suppress the uptake of phallotoxins completely. Several compounds known to inhibit the bile acid transport reduce the phallotoxin uptake to a similar degree. Hepatocytes exposed to reagents reacting preferentially with amino groups of proteins lose their uptake of both bile acids and phallotoxins. In hepatocytes isolated from 5 day old rats the uptake of both phallotoxins and cholate is reduced as compared to cells from adult controls. AS-30D ascites hepatoma cells, known to be insensitive to phallotoxins are unable to take up both phallotoxins and cholate. The results are consistent with our working hypothesis of a very similar mechanism for the uptake of bile acids and phallotoxins.

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References

  • Agostini, B., Govindan, U. M.: Elektronenmikroskopische Untersuchungen an der Zellmembran der Leber bei Phalloidin-Vergiftung. Verh. Dtsch. Ges. Pathol. 57, 436 (1973)

    Google Scholar 

  • Agostini, B., Govindan, U. M., Hofmann, W.: Morphological changes induced by phalloidin in the rat liver. In: Pathogenesis and mechanisms of liver cell necrosis. Keppler, D. (ed.), pp. 175–192. Lancaster U.K.: MTP-Press 1975

    Google Scholar 

  • Anwer, M. S., Hegner, D.: Interaction of fusidates with bile acid uptake by isolated rat hepatocytes. Naunyn-Schmiedeberg's Arch. Pharmacol. 302, 329–332 (1978a)

    Google Scholar 

  • Anwer, M. S., Hegner, D.: Effect of Na+ on bile acid uptake by isolated rat hepatocytes. Evidence for a heterogenous system. Hoppe-Seylers Z. Physiol. Chem. 359, 181–192 (1978b)

    Google Scholar 

  • Anwer, M. S., Kroker, R., Hegner, D.: Cholic acid uptake into isolated rat hepatocytes. Hoppe-Seylers Z. Physiol. Chem. 357, 1477–1486 (1976)

    Google Scholar 

  • Anwer, M. S., Kroker, R., Hegner, D.: Inhibition of hepatic uptake of bile acids by rifampicin. Naunyn-Schmiedebergs Arch. Pharmacol. 302, 19–24 (1978)

    Google Scholar 

  • Berry, M. N., Friend, D.S.: High-yield preparation of isolated rat liver parenchymal cells. J. Cell. Biol. 43, 506–529 (1969)

    Google Scholar 

  • Cabantchik, Z. I., Rothstein, A.: Membrane proteins related to anion permeability of human red blood cells. I. Localization of disulfonic stilbene binding sites in proteins involved in permeation. J. Membr. Biol. 15, 207–226 (1974)

    Google Scholar 

  • Faulstich, H., Wieland, Th., Schimassek, H., Walli, A. K., Ehler, N.: Mechanism of phalloidin intoxication II. Binding studies. In: Membrane alterations as basis of liver injury. Popper, H., Bianchi, L., Reutter, W. (eds.), pp. 301–310. Lancaster U.K.: MTP-Press 1976

    Google Scholar 

  • Fortes, P. A. G., Hoffmann, J. F.: The interaction of fluorescent probes with anion permeability pathways of human red cells. J. Membr. Biol. 16, 79–100 (1974)

    Google Scholar 

  • Frimmer, M., Petzinger, E., Rufeger, U., Veil, L. B.: The role of bile acids in phalloidin poisoning. Naunyn-Schmiedebergs Arch. Pharmacol. 301, 145–147 (1977)

    Google Scholar 

  • Gabbiani, G., Montesano, R., Tuchweber, B., Salas, M., Orci, L.: Phalloidin-induced hyperplasia of actin filaments in rat hepatocytes. Lab. Invest. 33, 562–569 (1975)

    Google Scholar 

  • Govindan, U. M., Rohr, G., Wieland, Th., Agostini, B.: Binding of a phallotoxin to protein filaments of plasma membrane of liver cell. Hoppe-Seylers Z. Physiol. Chem. 354, 1159–1161 (1973)

    Google Scholar 

  • Grundmann, E., Petzinger, E., Frimmer, M., Boschek, G.: A possible reason for the phalloidin tolerance of hepatoma cells. Naunyn-Schmiedebergs Arch. Pharmacol. 305, 253–259 (1978)

    Google Scholar 

  • Kroker, R., Anwer, A. S., Hegner, D.: The lack of active bile acid transport in AS-30D hepatoma cells. Naunyn-Schmiedebergs Arch. Pharmacol. 303, 299–301 (1978)

    Google Scholar 

  • Löw, I., Wieland, Th.: The interaction of phalloidin, some of its derivatives and of other cyclic peptides with muscle actin as studied by viscosimetry. FEBS Lett. 44, 340–343 (1974)

    Google Scholar 

  • Petzinger, E., Frimmer, M.: Studies on the phalloidin recognizing structure of the livercell surface. Naunyn-Schmiedebergs Arch. Pharmacol. 302 (Suppl.), R 18 (1978)

    Google Scholar 

  • Petzinger, E., Grundmann, E., Veil, L. B., Frimmer, M., Fasold, H.: Inhibitory effects of 4,4′-diisothiocyano-stilbene-2,2′-disulfonic acid (DIDS) in the response of isolated hepatocytes to phalloidin. Naunyn-Schmiedebergs Arch. Pharmacol. 304, 303–307 (1978)

    Google Scholar 

  • Petzinger, E., Frimmer, M., Ziegler, K.: Inhibition of 3H-demethylphalloin uptake in isolated rat hepatocytes under various experimental conditions. Naunyn-Schmiedebergs Arch. Pharmacol. 307, 275–281 (1979)

    Google Scholar 

  • Puchinger, H., Wieland, Th.: Suche nach einem Metaboliten bei Vergiftung mit Desmethylphalloin (DMP). Eur. J. Biochem. 11, 1–6 (1969)

    Google Scholar 

  • Rufeger, U., Grundmann, E.: Comparative studies on the sensitivity to phalloidin of normal hepatocytes and AS-30D hepatoma cells. Naunyn-Schmiedebergs Arch. Pharmacol. 297 (Suppl. II), R 17 (1977)

    Google Scholar 

  • Schwarz, L. R., Burr, R., Schwenk, R., Pfaff, E., Greim, H.: Uptake of taurocholic acid into isolated rat liver cells. Eur. J. Biochem. 55, 617–623 (1975)

    Google Scholar 

  • Snow, J. W., Brandts, J. F., Low, P.S.: The effects of anion transport inhibitors on structural transitions in erythrocyte membranes. Biochim. Biophys. Acta 512, 579–591 (1978)

    Google Scholar 

  • Stockem, W., Weber, K., Wehland, J.: The influence of microinjected phalloidin on locomotion, protoplasmic streaming and cytoplasmic organization in Amoeba proteus and Physarum polycephalum. Cytobiologia 18, 114–131 (1978)

    Google Scholar 

  • Wehland, J., Osborn, M., Weber, K.: Phalloidin-induced actin polymerization in the cytoplasm of cultured cells interferes with cell locomotion and growth. Proc. Natl. Acad. Sci. USA 74, 5613–5617 (1977)

    Google Scholar 

  • Wieland, O., Szabados, A.: On the nature of phalloidin tolerance in newborn rats. Adv. Clin. Biochem. Res. 4, 59–66 (1968)

    Google Scholar 

  • Wieland, Th., Govindan, U. M.: Phallotoxin bind to actins. Febs Lett. 46, 351–353 (1974)

    Google Scholar 

  • Wieland, Th., Faulstich, H.: Amatoxins, phallotoxins, phallolysin and antamanide: The biologically active components of poisoneous amanita mushrooms. CRC Crit. Rev. Biochem. 5, 185–260 (1978)

    Google Scholar 

  • Ziegler, K., Petzinger, E., Grundmann, E., Frimmer, M.: Decreased sensitivity of isolated hepatocytes from baby rats, from regenerating and from poisoned liver against phalloidin. Naunyn-Schmiedebergs Arch. Pharmacol. 306, 295–300 (1979)

    Google Scholar 

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Authors and Affiliations

  1. Institut für Pharmakologie und Toxikologie im FB 18, Justus-Liebig-Universität Giessen, Frankfurter Strasse 107, D-6300, Giessen, Federal Republic of Germany

    E. Petzinger & M. Frimmer

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  1. E. Petzinger
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  2. M. Frimmer
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This work was supported by the Deutsche Forschungsgemeinschaft

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Petzinger, E., Frimmer, M. Comparative studies on the uptake of 14C-bile acids and 3H-demethylphalloin in isolated rat liver cells. Arch. Toxicol. 44, 127–135 (1980). https://doi.org/10.1007/BF00303189

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  • DOI: https://doi.org/10.1007/BF00303189

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