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  • Historical Perspective
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One hundred years of membrane permeability: does Overton still rule?

Abstract

The Overton Rule states that entry of any molecule into a cell is governed by its lipid solubility. Overton’s studies led to the hypothesis that cell membranes are composed of lipid domains, which mediate transport of lipophilic molecules, and protein ‘pores’, which transport hydrophilic molecules. Recent studies, however, have shown that hydrophobic molecules are also transported by families of transporter proteins.

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References

  1. Overton, E. Vierteljahrsschr. Naturforsch. Ges. Zurich. 44, 88–135 (1899).

    Google Scholar 

  2. Kepner, G. R. (ed.) in Cell Membrane Permeability and Transport 29–56 (Dowden, Hutchins & Ross, Stroudsberg, PA, 1979).

    Google Scholar 

  3. Collander, R. Trans Faraday Soc. 33, 985–990 (1949).

    Article  Google Scholar 

  4. Höber, R. Physiol. Rev. 16, 52–102 (1936).

    Article  Google Scholar 

  5. Davson, H. & Danielli, J.F. The Permeability of Natural Membranes (Cambridge Univ. Press, Cambridge, 1943).

    Google Scholar 

  6. Singer S. J. & Nicolson, G. L. Science 175, 720–731 (1972).

    Article  CAS  Google Scholar 

  7. Lieb, W. R. & Stein, W. D. Curr. Top. Membr. Transp. 2, 1–39 (1971).

    CAS  Google Scholar 

  8. Orbach, E. & Finkelstein, A. J. Gen. Physiol. 75, 427–436 (1980).

    Article  CAS  Google Scholar 

  9. Finkelstein, A. Water Movement Through Lipid Bilayers, Pores, and Plasma Membranes: Theory and Reality (Soc. Gen. Physiol., Woods Hole, MA, 1987).

    Google Scholar 

  10. Hays, R. M. & Leaf, A. J. Gen. Physiol. 45, 905–919 (1962).

    Article  CAS  Google Scholar 

  11. Gluck, S. & Al-Awqati, Q. Nature 284, 631–632 (1980).

    Article  CAS  Google Scholar 

  12. Pietras, R. J. & Wright, E. M. Nature 247, 222–224 (1974).

    Article  CAS  Google Scholar 

  13. Preston, G. M., Carroll, T. P., Guggino, W. B. & Agre, P. Science 256, 385–387 (1992).

    Article  CAS  Google Scholar 

  14. Fushimi, K. et al. Nature 361, 549–552 (1993).

    Article  CAS  Google Scholar 

  15. Tsukaguchi, H., Shayakul, C., Berger, U. V. & Hediger, M. A. Am. J. Physiol. 275, F319–F324 (1998).

    CAS  PubMed  Google Scholar 

  16. Cooper, G. J. & Boron, W. F. Am. J. Physiol. 275, C1481–C1486 (1998).

    Article  CAS  Google Scholar 

  17. Singh, S. K., Binder, H. J., Geibel, J. P. & Boron W. F. Proc. Natl Acad. Sci. USA 92, 11573–11577 (1995).

    Article  CAS  Google Scholar 

  18. Bohr, C. J. Physiol. (Lond). 15, 494–500 (1894).

    Article  CAS  Google Scholar 

  19. Price, N. T., Jackson, V. N. & Halestrap, A. P. Biochem. J. 329, 321–328 (1998).

    Article  CAS  Google Scholar 

  20. Kanai, N. et al. Science 268, 866–869 (1995).

    Article  CAS  Google Scholar 

  21. Hirsch, D., Stahl, A. & Lodish, H. F. Proc. Natl Acad. Sci. USA 95, 8625–8629 (1998).

    Article  CAS  Google Scholar 

  22. Ruetz, S. & Gros, P. Cell 77, 1071–1081 (1994).

    Article  CAS  Google Scholar 

  23. van Helvoort, A. et al. Cell 87, 507–517 (1996).

    Article  CAS  Google Scholar 

  24. Scott, J. Nature 400, 817–818 (1999).

    Article  Google Scholar 

  25. Garcia, C. K. et al. Cell 76, 865–873 (1994).

    Article  CAS  Google Scholar 

  26. Tsukaguchi, H. et al. Nature 399, 70–75 (1999).

    Article  CAS  Google Scholar 

  27. Koepsell, H., Gorboulev, V. & Arndt, P. J. Membr. Biol. 167, 103–117 (1999).

    Article  CAS  Google Scholar 

  28. Roch‐Ramel, F. Curr. Opin. Nephrol. Hypertens. 7, 517–524 (1998).

    Article  Google Scholar 

  29. Simons, K. & Ikonen, E. Nature 387, 569–572 (1997).

    Article  CAS  Google Scholar 

  30. Dainty, J. & House, C. R. J. Physiol. (Lond.) 182, 66–78 (1966).

    Article  CAS  Google Scholar 

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Correspondence to Qais Al-Awqati.

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Al-Awqati, Q. One hundred years of membrane permeability: does Overton still rule?. Nat Cell Biol 1, E201–E202 (1999). https://doi.org/10.1038/70230

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