Advertisement

The Puzzle of Rates of Cellular Uptake of Protein-Bound Ligands

  • Ludvik Bass
  • Susan M. Pond
Part of the NATO ASI Series book series (NSSA, volume 145)

Abstract

The rates of hepatic and cerebral uptake of physiologically important ligands, such as fatty acids, drugs and dyes, have long been known to be surprisingly high when most ligand is bound to plasma proteins (Baker & Bradley, 1966, Pardridge & Landaw, 1984). The magnitudes of these rates, as well as the unexpected forms of their dependence on protein concentration, have motivated the hypothesis of specific albumin receptors on the hepatocyte (Weisiger, Gollan & Ockner, 1981) helping to translocate the ligand from albumin into the cell; and the hypothesis of a catalytic mechanism of dissociation of ligand from protein at the cellular surface (for example, Baker & Bradley, 1966; Forker & Luxon, 1981). We shall refer to both proposals as facilitation hypotheses. We do not include in this term facilitation of cellular uptake of unbound ligands (see for example Stremmel, Strohmeyer & Berk, 1986).

Keywords

Albumin Concentration Hepatic Uptake Unstirred Layer Intact Liver Unbind Ligand 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Arias, I.M., Popper, H., Schachter, D. &Shafritz, D.A. (1982). The Liver. New York: Raven Press.Google Scholar
  2. Baker, K.J. &Bradley, S.E.(I966). J. Clin. Invest. 43, 281.CrossRefGoogle Scholar
  3. Barnhart, J.L., Witt, B.L., Hardison, W.G. &Berk, R.N.(1983). Am. J. Physiol. 244, G 630.Google Scholar
  4. Barry, P.H. &Diamond, J.M.(I984). Physiol. Rev. 64, 763.PubMedGoogle Scholar
  5. Bass, L.(I985). Circulation 72 (Suppl. IV), 47.Google Scholar
  6. Bass, L.(1986). J. Pharm. Sci. 75, 321.PubMedCrossRefGoogle Scholar
  7. Bass, L. &Pond, S.M.(1986). Applied Mathematics Preprint No. 123. University of Queensland(ISBN 0 86776 222 5).Google Scholar
  8. Brauer, R.W.,Leong, G.F., McElroy, R.F. &Holloway, R.J.(1956). Am. J. Physiol. 184. 593.PubMedGoogle Scholar
  9. Boyer,J.L., Schwarz,J. &Smith, N.(I976). Am. J. Physiol. 230(4), 974.PubMedGoogle Scholar
  10. Byrne, A.J., Morgan, D.J., Harrison, P.M. &McLean, A.J.(1985). J. Pharm. Sci. 74, 205.PubMedCrossRefGoogle Scholar
  11. Dixon, M. &Webb, E.C.(I979). Enzymes (3rd edition). London:Longman.Google Scholar
  12. Fleischer, A.B., Shurmantine, W.O., Luxon, B.A. &Forker, E.L.(1986). J. Clin. Invest. 77, 964.PubMedCrossRefGoogle Scholar
  13. Forker, E.L. &Luxon, B.A.(1981). J. Clin. Invest. 67, 1517.PubMedCrossRefGoogle Scholar
  14. Forker, E.L., Luxon, B.A., Snell, M. &Shurmantine, W.O.(1982). J. Pharmacol. Exp. Ther. 223, 342.PubMedGoogle Scholar
  15. Forker, E.L. &Luxon, B.A.(1985). Hepatology 5, 1236.PubMedCrossRefGoogle Scholar
  16. Gillette, J.R.(1971). Ann. N.Y. Acad. Sci. 179, 43.PubMedCrossRefGoogle Scholar
  17. Jones, D.B., Morgan, D.J., Mihaly, G.W., Webster, L.K. &Smallwood, R.A.(1984). J. Pharmacol. Exp. Ther. 229, 522.PubMedGoogle Scholar
  18. Mizuma, T., Horie, T., Hayashi, M. &Awazu, S.(1986). J. Pharmacobio-Dyn. 9, 244.PubMedCrossRefGoogle Scholar
  19. Noy, N., Donnelly, T.M. &Zakim, D.(I986). Biochemistry 25. 2013.PubMedCrossRefGoogle Scholar
  20. Nunes, R., Kiang, L. &Berk, P.D.(1985). Hepatology 5, 1035 (abstract).Google Scholar
  21. Oie, S. &Fiori, F.(I985). J. Pharmacol. Exp. Ther. 234, 636.PubMedGoogle Scholar
  22. Pang, K.S. &Rowland, M.(1977). J. Pharmacokin. Biopharm. 5, 625.Google Scholar
  23. Pardridge, W.M., &Landaw, E.M.(I984). J. Clin. Invest. 74, 746.CrossRefGoogle Scholar
  24. Rowland, M., Leitch, D., Fleming, G. &Smith, B.(1984). J. Pharmacokin. Biopharm. 12, 129.Google Scholar
  25. Stremmel, W., Strohmeyer, G. &Berk, P.D.(1986). Proc. Natl. Acad. Sci. USA 83, 3584.PubMedCrossRefGoogle Scholar
  26. Svenson, A., Holmer, E. &Andersson, L-O.(1974). Biochem. Biophys. Acta. 342, 54.PubMedCrossRefGoogle Scholar
  27. Weisiger, R.A., Gollan, J. &Ockner, R.(1981). Science 211, 1048.PubMedCrossRefGoogle Scholar
  28. Weisiger, R.A., Gollan, J. &Ockner, R.(1982). Progress in Liver Disease 7, 71.Google Scholar
  29. Weisiger, R.A., Zacks, C.M., Smith, N.D. &Boyer, J.L.(1984). Hepatology 4, 492.PubMedCrossRefGoogle Scholar
  30. Weisiger, R.A. &Ma, W-L.(1985). Hepatology 5. 1012 (abstract).Google Scholar
  31. Weisiger, R.A.(1985). Proc. Natl. Acad. Sci. USA, 82, 1563.PubMedCrossRefGoogle Scholar
  32. Weisiger, R.A. &Ma, W-L.(in press). J. Clin. Invest.Google Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Ludvik Bass
    • 1
  • Susan M. Pond
    • 1
  1. 1.Departments of Mathematics and MedicineUniversity of QueenslandBrisbaneAustralia

Personalised recommendations