Advertisement

Gastroenterologia Japonica

, Volume 11, Issue 1, pp 23–30 | Cite as

Influence of drugs and chemicals upon hepatic enzymes and proteins. II. The effects of various barbiturates on the induction and reduction of hepatic cytoplasmic organic anion-binding proteins

  • Yukihiko Adachi
  • Toshio Yamamoto
Original Article

Summary

The effects of seven barbiturates (phenobarbital, three N-phenylbarbiturates and three N-cyclohexylbarbiturates) on the hepatic cytoplasmic organic anion-binding proteins, Y and Z, were investigated in an attempt to observe the structure-activity relationship of baributrates to induction and reduction of these two proteins. Sulfobromophthalein (BSP) was fully bound by the Y and Z proteins at ten minutes of mixing with the 10,5000 X g supernate. In low concentrations of BSP, saturation of binding of BSP by the Z protein was very low, and with increasing concentration, BSP-binding by the Z protein increased rapidly. The Y protein bound BSP sufficiently even in low concentrations of the dye. BSP-binding capacity of the Y protein was increased by phenobarbital, phetharbital and bucolome, and decreased by one of the N-phenylbarbiturates. BSP-binding capacity of the Z protein tended to be decreased by phenobarbital and phetharbital, but to be increased by bucolome. The other N-phenyl and N-cyclohexylbarbiturates had no effect on the binding capacities of the two proteins. From these results, it was concluded that the regulation by the barbiturates of cytoplasmic proteins is different from that of the microsomal enzymes, and that both type and structural relation are important in the induction and reduction of the Y and Z proteins.

Key words

barbiturates organic anion-binding proteins Y protein ligandin Z protein sulfobromophthalein 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1).
    Goresky, CA.: The hepatic uptake and excretion of sulfobromophthalein and bilirubin. Can. Med. Assoc. J. 92: 851–857, 1965.PubMedGoogle Scholar
  2. 2).
    Goresky, C.A. and Bach, C.G.: Membrane transport and the hepatic circulation. Ann. N.Y. Acad. Sci. 170: 18–7, 1970.CrossRefGoogle Scholar
  3. 3).
    Cornelius, C.E., Ben-Ezzer, J. and Arias, I.M.: Binding of organic anions by rat liver plasma membranes in vitro. Proc. Soc. Exp. Biol. Med. 124: 665–667, 1967.PubMedGoogle Scholar
  4. 4).
    Levi, A.J., Gatmaitan, Z. and Arias, I.M.: Two hepatic cytoplasmic protein fractions, Y and Z, and their possible role in the hepatic uptake of bilirubin, sulfobromophthalein, and other anions. J. Clin. Invest. 48: 2156–2167, 1969.PubMedGoogle Scholar
  5. 5).
    Litwack, G., Ketterer, B. and Arias, I.M.: Ligandin: a hepatic protein which binds bilirubin, carcinogens and a number of exogeneous organic anions. Nature (Lond) 234: 466–467, 1971.CrossRefGoogle Scholar
  6. 6).
    Reyes, H., Levi, A.J., Gatmaitan, Z. and Arias, I.M.: Studies of Y and Z, two hepatic cytoplasmic organic anion-binding proteins: effect of drugs, chemicals, hormons and cholestasis. J. Clin. Invest. 50: 2242–2252, 1971.PubMedGoogle Scholar
  7. 7).
    Fleishner, G., Robbins, J. and Arias, I.M.: Immunological studies of Y protein, a major cytoplasmic organic anion-binding protein in rat liver. J. Clin. Invest. 51: 677–684, 1972.Google Scholar
  8. 8).
    Reyes, H., Levi, A.J., Gatmaitan, Z. and Arias, I.M.: Organic anion-binding protein in rat liver: drug induction and its physiologic consequence. Proc. Nat. Acad. Sci. 61: 168–170, 1969.CrossRefGoogle Scholar
  9. 9).
    Hunter, J., Thompson, R.P.H., Rake, M.O. and Williams, R.: Controlled trial of phetharbital, a non-hypnotic barbiturate, in unconjugated hyperbilirubinemia. Br. Med. J. 2: 497–499, 1971.PubMedCrossRefGoogle Scholar
  10. 10).
    Yamamoto, T. and Sakamoto, K.: Treatment of constitutional unconjugated hyperbilirubinemia. Acta Hepatol. Jap. 12: 173–174, 1971. (in Japanese)Google Scholar
  11. 11).
    Lowry, O.H., Rosebough, N.J., Farr, A.L. and Randall, R.J.: Protein measurement with Folin phenol reagent. J. Biol. Chem. 193: 265–275, 1951.PubMedGoogle Scholar
  12. 12).
    Miller, G.L.: Protein determination for large numbers of samples. Anal. Chem. 31: 964, 1959.CrossRefGoogle Scholar
  13. 13).
    Kenwright, S. and Levi, A.J.: Sites of competition in the selective hepatic uptake of rifamycin-SV, flavaspidic acid, bilirubin and bromsulphthalein. Gut 15: 220–226, 1974.PubMedCrossRefGoogle Scholar
  14. 14).
    Kenwright, S. and Levi, A.J.: Impairment of hepatic uptake of rifamycin antibiotics by probenecid, and its therapeutic implications. Lancet 2: 1402–1405, 1973.Google Scholar
  15. 15).
    Habig, W.H., Pabst, M.J., Fleishner, G., Gatmaitan, Z., Arias, I.M. and Jacoby, W.B.: The identity of glutathione S-transferase B with ligandin, a major binding protein of the liver. Proc. Nat. Acad. Sci. 71: 3879–3882, 1974.PubMedCrossRefGoogle Scholar
  16. 16).
    Adachi, Y. and Yamamoto, T.: Influence of drugs and chemicals upon hepatic enzymes and proteins. I. Structure-activity relationship of various barbiturates to microsomal enzyme induction in rat liver. Biochem. Pharmacol. 25:663–668, 1976.PubMedCrossRefGoogle Scholar
  17. 17).
    Yamamoto, T. and Adachi, Y.: On the mechanism of the effect of bucolome on hyperindirectbilirubinemia. Acta Hepatol. Jap. 15: 607, 1974. (in Japanese)Google Scholar

Copyright information

© The Japanese Society of Gastroenterology 1976

Authors and Affiliations

  • Yukihiko Adachi
    • 1
  • Toshio Yamamoto
    • 1
  1. 1.Department of MedicineKinki University School of MedicineOsakaJapan

Personalised recommendations