Identification of Carrier Proteins in Hepatocytes by (Photo) Affinity Labels Derived from Foreign Cyclopeptides

  • K. Ziegler
Conference paper
Part of the Proceedings in Life Sciences book series (LIFE SCIENCES)


Certain cyclopeptides of toxicological (e.g. phallotoxins) or pharmacological interest (e.g. antamanide, cyclosomatostatins) are rapidly eliminated via the biliary pathway (Frimmer 1987, Caldwell 1984). A liver-specific clearance mechanism is responsible for the hepatospecific toxic effects of e.g. phallotoxins and for the short half life of cyclosomatostatins. We did not expect a carrier-mediated uptake to be responsible for this first-pass elimination. The transport of various cyclopeptides is driven by a sodium gradient and the membrane potential (Review by Frimmer and Ziegler 1988). By mutual competition experiments it became evident that bile acids are the physiological substrates of this transport system. Actually, the carrier seems to be unable to discriminate between various structurally different compounds like bile acids and cyclopeptides. It was therefore termed a “multispecific transporter” (Ziegler et al. 1985).


Bile Acid Basolateral Plasma Membrane Photoaffinity Label Bile Acid Transporter Isolate Plasma Membrane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Caldwell LJ, Parr A, Beihn RM, Agha BJ, Mlodozemiec AR, Jay M, Digenis GA (1985) Drug distribution and biliary excretion pattern of a cyclic somatostatin analog. Pharmaceut Res 2: 55–96CrossRefGoogle Scholar
  2. Frimmer M (1987) What we have learned from phalloidin. Toxicol Lett 35: 169–183PubMedCrossRefGoogle Scholar
  3. Frimmer M, Ziegler K (1988) The transport of bile acids in liver cells. Biochim Biophys Acta 947: 75–99PubMedGoogle Scholar
  4. Kessler H, Haupt A, Frimmer M, Ziegler K (1987) Synthesis of a cyclic retro analogue of somatostatin suitable for photoaffinity labeling. Int J Peptide Protein Res 29: 621–628CrossRefGoogle Scholar
  5. Schade RR, Guglielmi A, van Thiel DH, Thompson ME, Warty V, Griffith B, Sanghri A, Bahnson H, Hardesty R (1983) Cholestasis in heart transplant recipients treated with cyclosporine. Transplant Proc 4: 2757–2760Google Scholar
  6. Wieland T, Nassal M, Kramer W, Fricker. G, Bickel U, Kurz G (1984) Identity of hepatic membrane transport systems for bile salts, phalloidin and antamanide by photoaffinity labeling. Proc Natl Acad Sci USA 81: 5232–5236PubMedCrossRefGoogle Scholar
  7. Ziegler K, Frimmer M, Kessler H, Damm J, Eiermann V, Koll S, Zarbock J (1985) Modified somatostatins as inhibitors of a multispecific transport system for bile acids and phallotoxin in isolated hepatocytes. Biochim Biophys Acta 845: 86–93PubMedCrossRefGoogle Scholar
  8. Ziegler K, Frimmer M (1986a) Cyclosporin A and a diaziridine derivative inhibit the hepatocellular uptake of cholate, phalloidin and rifampicin. Biochim Biophys Acta 855: 136–142PubMedCrossRefGoogle Scholar
  9. Ziegler K, Frimmer M (1986b) Identification of cyclosporin binding sites in rat liver plasma membranbes, isolated hepatocytes and hepatoma cells by photoaffinity labelinq using (3H) cyclosporin-diazirine. Biochim Biophys Acta 855: 147–156PubMedCrossRefGoogle Scholar
  10. Ziegler K, Polzin G, Frimmer M (1988a) Hepatocellular uptake of cyclosporine A by simple diffusion Biochim Biophys Acta 938: 44–50PubMedCrossRefGoogle Scholar
  11. Ziegler K, Frimmer M, Kessler H, Haupt A (1988b) Azidobenzamido c(Phe-Thr-Lys-Trp-Phe-DPro), a new photosensitive substrate for the “multispecific bile acid transporter” of hepatocytes: Evidence for a common transport system for bile acids and cyclosomatostatins in basolateral membranes. Biochim Biophys Acta (submitted)Google Scholar
  12. Ziegler K, Frimmer M, Milliner S, Fasold H (1988c) Identification of bile acid binding proteins in hepatocellular membranes of newborn and adult rats. Biochim Biophys Acta (submitted)Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • K. Ziegler
    • 1
  1. 1.Institut für Pharmakologie und ToxikologieJustus-Liebig-UniversitätGiessenBRD

Personalised recommendations