Summary
Isolated hepatocytes, prepared from 5 day old rats, from regenerating livers or from livers after poisoning with carbon tetrachloride, are less sensitive to phalloidin in vitro than hepatocytes from untreated adult controls. The time course of the reduced susceptibility to phalloidin was compared with the ability of hepatocytes to take up bile acids under various conditions. SDS-electrophoresis of cell lysates gave no evidence for decreased levels of actin in cells with reduced sensitivity to phalloidin. In contrast, there was a good relationship between the active uptake of bile acids and the sensitivity of hepatocytes to phalloidin. The decreased response of hepatocytes from baby rats, from regenerating livers or from poisoned livers to phalloidin is more probably related to differences in phalloidin uptake than to a reduced endowment with microfilamentous structures.
Similar content being viewed by others
References
Agostini, B., Govindan, M. V.: Elektronenmikroskopische Untersuchungen an der Zellmembran der Leber bei Phalloidin-Vergiftung. Verh. Dtsch. Ges. Path. 57, 436 (1973)
Anwer, M. S., Hegner, D.: Interaction of fusidates with bile acid uptake by isolated rat hepatocytes. Naunyn-Schmiedeberg's Arch. Pharmacol. 302, 329–332 (1978)
Anwer, M. S., Kroker, R., Hegner, D.: Cholic acid uptake into isolated rat hepatocytes. Hoppe-Seylers Z. Physiol. Chem. 357, 1477–1486 (1976)
Anwer, M. S., Kroker, R., Hegner, D.: Inhibition of hepatic uptake of bile acids by rifampicin. Naunyn-Schmiedeberg's Arch. Pharmacol. 302, 19–24 (1978)
Clarke, M., Spudich, J. A.: Biochemical and structural studies of actomysin-like proteins from non-muscle cells. J. Mol. Biol. 86, 209–222 (1974)
Decken, A. von der, Löw, H., Hultin, T.: Über die primären Wirkungen von Phalloidin von Leberzellen. Biochem. Z. 332, 503–518 (1960)
Degkwitz, E., Köhler, F. R., Staudinger, H.: Aktivitätsänderungen von einigen mikrosomalen Leberenzymen nach Phalloidinvergiftung bei Ratten. Hoppe-Seyler's Z. Physiol. Chem. 35, 1023–1026 (1969)
Faulstich, H., Wieland, Th., Schimassek, H., Walli, A. K., Ehler, N.: Mechanism of phalloidin intoxication. II. Binding studies. In: Membrane alteration as basis of liver injury (H. Popper, L. Bianchi, and W. Reutter, eds.), pp. 301–310. Lancaster, U.K.: MTP Press Ltd 1977
Fiume, L.: Mechanism of action of phalloidin. Lancet 12, 1284 (1965)
Floersheim, G. L.: Schutzwirkung hepatotoxischer Stoffe gegen letale Dosen aus Amanita phalloides (Phalloidin). Biochem. Pharmacol. 15, 1589–1593 (1966)
Floersheim, G. L.: Protection by phalloidin against lethal doses of phalloidin. Agents Actions 6, 490–492 (1976)
Frimmer, M., Petzinger, E.: Mechanism of phalloidin intoxication. I. Cell membrane alterations. In: Membrane alterations as basis of liver injury (H. Popper, L. Bianchi, and W. Reutter, eds.), pp. 293–299. Lancaster, U.K.: MTP Press Ltd. 1977
Frimmer, M., Schischke, B.: Decreased toxicity of phalloidin in partially hepatectomized rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 272, 447–449 (1972)
Frimmer, M., Kroker, R., Porstendörfer, J.: The mode of action of phalloidin: Demonstration of rapid deformation of isolated hepatocytes by scanning electron microscopy. Naunyn-Schmiedeberg's Arch. Pharmacol. 284, 395–398 (1974)
Frimmer, M., Petzinger, E., Homann, J.: Phalloidin-Antagonisten. 4. Mitteilung: Thioctsäure, SH-Verbindungen, Rifampicin, Choleretika, Dexamethason, Östradiol, unspezifische Hemmstoffe und unwirksame Verbindungen. Arzneim.-Forsch. (Drug Res.) 25, 1881–1884 (1975)
Frimmer, M., Petzinger, E., Rufeger, U., Veil, L. B.: Trypsin protection of hepatocytes agaist phalloidin. Naunyn-Schmiedeberg's Arch. Pharmacol. 300, 169–171 (1977a)
Frimmer, M., Petzinger, E., Rufeger, U., Veil, L. B.: The role of bile acids in phalloidin poisoning. Naunyn-Schmiedeberg's Arch. Pharmacol. 301, 145–147 (1977b)
Govindan, V. M., Faulstich, H., Wieland, Th.: In vitro effect of phalloidin on a plasma membrane preparation from rat liver. Naturwissenschaften 59, 521–522 (1972)
Grundmann, E., Petzinger, E., Frimmer, M., Boschek, C. B.: A possible reason for the phalloidin tolerance of hepatoma cells. Naunyn-Schmiedeberg's Arch. Pharmacol. 305, 253–259 (1978)
Harris, H. E., Tso, M. Y. W., Epstein, H. F.: Actin and myosinlinked calcium regulation in the nematode Caenorhabditis elegans. Biochemical and structural properties of native filaments and purified protein. Biochemistry 16, 859–865 (1977)
Higgins, G. M., Anderson, R. M.: Experimental pathology of the liver. I. Restoration of the liver of the white rat following partial surgical removal. Arch. Path. 12, 186–202 (1931)
Kroker, R., Anwer, A. S., Hegner, D.: The lack of active bils acid transport in AS-30D hepatoma cells. Naunyn-Schmiedeberg's Arch. Pharmacol. 303, 299–301 (1978)
Lutz, F., Herrmann, S., Frimmer, M.: The influence of sodium dehydrocholate on the uptake of 3H-desmethylphalloin by the perfused rat liver. Naunyn-Schmiedeberg's Arch. Pharmacol. 270, 310–312 (1971)
Matschinsky, F., Meyer, U., Wieland, O.: Die Wirkung des Knollenblätterpilzgiftes Phalloidin auf die isolierte Rattenleber. Biochem. Z. 333, 48–61 (1960)
Pelley, J. W., Garner, C. W., Little, G. H.: A simple rapid biuret method for the estimation of protein in samples containing thiols. Ann. Biochem. 86, 341–343 (1978)
Petzinger, E., Frimmer, M.: Studies on the phalloidin recognizing structure of the liver cell surface. Naunyn-Schmiedeberg's Arch. Pharmacol. 302, R 18 (1978)
Petzinger, E., Seeger, R.: Scanning electron microscopic studies on the cytolytic effect of phallolysin on isolated rat hepatocytes and AS-30D hepatoma cells. Naunyn-Schmiedeberg's Arch. Pharmacol. 295, 211–213 (1976)
Petzinger, E., Homann, J., Frimmer, M.: Phalloidin-Antagonisten. 2. Mitteilung: Protektive Wirkung von Disilybin bei Vergiftung isolierter Hepatozyten mit Phalloidin. Arzneim.-Forsch. (Drug Res.) 25, 571–576 (1975)
Petzinger, E., Grundmann, E., Veil, L. B., Frimmer, M., Fasold, H.: Inhibitory effects of 4,4′-diisothiocyano-stilbene-2,2′-disulfonic acid (DIDS) in phalloidin response of isolated hepatocytes. Naunyn-Schmiedeberg's Arch. Pharmacol. 304, 393–307 (1978)
Petzinger, E., Ziegler, K., Frimmer, M.: Inhibition of 3H-demethylphalloin uptake in isolated rat hepatocytes after various treatments and experimental manipulations. Naunyn-Schmiedeberg's Arch. Pharmacol. (In press, 1979)
Puchinger, H.: Zum Wirkungsmechanismus von Phalloidin und Antamanid. Thesis, Frankfurt 1968
Puchinger, H., Wieland, Th.: Suche nach einem Metaboliten bei Vergiftung mit Desmethylphalloin (DMP). Eur. J. Biochem. 11, 1–6 (1969)
Schimassek, H., Jeckel, D.: Wirkung von Phalloidin auf Leberzellen: Bindung, Strukturveränderung und Elimination. Cytobiologie 17, 73–83 (1978)
Siess, E., Wieland, O., Miller, F.: Elektronenmikroskopische Untersuchungen zur Phalloidintoleranz neugeborener Ratten, Mäuse und Kaninchen. Virchows Arch., Abt. B Zellpath. 6, 151–165 (1970)
Szabados, A.: Zum Phänomen der Phalloidintoleranz neugeborener Ratten. Thesis, München 1971
Tuchweber, B., Kovacs, K., Khandekar, J. D., Garg, B. D.: Prevention of phalloidin intoxication in rats by partial hepatectomy. Arch. Toxicol. 29, 311–316 (1972)
Walli, A. K., Faulstich, H., Wieland, Th.: Diminished phallotoxin uptake in livers of newborn rats. Naunyn-Schmiedeberg's Arch. Pharmacol. (submitted for publication, 1979)
Wieland, O., Szabados, A.: On the nature of phalloidin tolerance in newborn rats. 6th Int. Congr. Clin. Chem., Munich 1966; Advances in Clinico-Biochemical Research, pp. 59–66. Basel-New York: Karger 1968
Author information
Authors and Affiliations
Additional information
This work is supported by the Deutsche Forschungsgemeinschaft
Rights and permissions
About this article
Cite this article
Ziegler, K., Petzinger, E., Grundmann, E. et al. Decreased sensitivity of isolated hepatocytes from baby rats, from regenerating and from poisoned livers to phalloidin. Naunyn-Schmiedeberg's Arch. Pharmacol. 306, 295–300 (1979). https://doi.org/10.1007/BF00507117
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00507117