Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Drug excretion mediated by a new prototype of polyspecific transporter

Abstract

CATIONIC drugs of different types and structures (antihistaminics, antiarrhythmics, sedatives, opiates, cytostatics and antibiotics, for example) are excreted in mammals by epithelial cells of the renal proximal tubules and by hepatocytes in the liverl–4. In the proximal tubules, two functionally disparate transport systems are involved which are localized in the basolateral and luminal plasma membrane and are different from the previously identified neuronal monoamine transporters and ATP-dependent multidrug exporting proteins1–3,5–12. Here we report the isolation of a complementary DNA from rat kidney that encodes a 556-amino-acid membrane protein, OCT1, which has the functional characteristics of organic cation uptake over the basolateral membrane of renal proximal tubules and of organic cation uptake into hepatocytes. OCT1 is not homologous to any other known protein and is found in kidney, liver and intestine. As OCT1 translocates hydrophobic and hydrophilic organic cations of different structures, it is considered to be a new prototype of polyspecific transporters that are important for drug elimination.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Roch-Ramel, F., Besseghir, K. & Murer, H. in Handbook of Physiology 8, Renal Physiology Vol. 2 (ed. Windhager, E. E.) 2189–2262 (Oxford Univ. Press, Oxford, 1992).

    Google Scholar 

  2. Ullrich, K. J. Biochim. biophys. Acta 1197, 45–62 (1994).

    Article  CAS  Google Scholar 

  3. Pritchard, J. B. & Miller, D. S. in The Kidney: Physiology and Pathophysiology (eds Seldin, D. W. & Giebisch, G.) 2921–2945 (Raven, New York, 1992).

    Google Scholar 

  4. Meijer, D. K. F., Mol, W. E. M., Müller, M. & Kurz, G. J. Pharmakin. Biopharmac. 18, 35–70 (1990).

    Article  CAS  Google Scholar 

  5. Schuldiner, S. J. Neurochem. 62, 2067–2078 (1994).

    Article  CAS  Google Scholar 

  6. Schloss, P., Mayser, W. & Betz, H. FEBS Lett. 307, 76–80 (1992).

    Article  CAS  Google Scholar 

  7. Gottesman, M. M. & Pastan, I. A. Rev. Biochem. 62, 385–427 (1993).

    Article  CAS  Google Scholar 

  8. Wright, S. H. & Wunz, T. M. Am. J. Physiol. 253, F1040–F1050 (1987).

    CAS  PubMed  Google Scholar 

  9. Montrose-Rafizadeh, C., Mingard, F., Murer, H. & Roch-Ramel, F. Am. J. Physiol. 257, F243–F251 (1989).

    CAS  PubMed  Google Scholar 

  10. Takano, M., Inui, K.-I., Okano, T., Saito, H. & Hori, R. Biochim. biophys. Acta 773, 113–124 (1984).

    Article  CAS  Google Scholar 

  11. Sokol, P. P. & McKinney, T. D. Am. J. Physiol. 258, F1599–F1607 (1990).

    CAS  PubMed  Google Scholar 

  12. Thiebaut, F. et al. J. Histochem. Cytochem. 37, 159–164 (1989).

    Article  CAS  Google Scholar 

  13. Ullrich, K. J., Papavassiliou, F., David, C., Rumrich, G. & Fritzsch, G. Pfluegers Arch. 419, 84–92 (1991).

    Article  CAS  Google Scholar 

  14. David, D., Rumrich, G. & Ullrich, K. J. Krongreβ der Gesellschaft für Nephrologie Hamburg. Abstr. 472 (Dustri, München, 1994).

    Google Scholar 

  15. Pacholczyk, T., Blakely, R. D. & Amara, S. G. Nature 350, 350–354 (1991).

    Article  ADS  CAS  Google Scholar 

  16. Schömig, E., Babin-Ebell, J. & Russ, H. Naunyn-Schmiedeberg's Arch. Pharmac. 347, 379–383 (1993).

    Article  Google Scholar 

  17. Magagnin, S. et al. J. biol. Chem. 267, 15384–15390 (1992).

    CAS  PubMed  Google Scholar 

  18. Kozak, M. Nucleic Acids Res. 12, 857–872 (1984).

    Article  CAS  Google Scholar 

  19. Hohage, H., Mörth, D. M., Querl. I. U. & Greven, J. Pharmac. Exp. Ther. 268, 897–901 (1994).

    CAS  Google Scholar 

  20. Gingrich, J. A. et al. FEBS Lett. 312, 115–122 (1992).

    Article  CAS  Google Scholar 

  21. Schömig, E. & Schönfeld, C.-L. Naunyn-Schmiedeberg's Arch. Pharmac. 341, 404–410 (1990).

    Article  Google Scholar 

  22. Trendelenburg, U. in Handbook of Experimental Pharmacology (eds Trendelenburg, U. & Weiner, N.) 279–319 (Springer, Berlin, 1988).

    Google Scholar 

  23. Russ, H., Gliese, M., Sonna, J. & Schömig, E. Naunyn-Schmiedeberg's Arch. Pharmac. 346, 158–165 (1992).

    Article  CAS  Google Scholar 

  24. Veyhl, M. et al. J. biol. Chem. 268, 25041–25053 (1993).

    CAS  PubMed  Google Scholar 

  25. Kyte, J. & Doolittle, R. F. J. molec. Biol. 157, 105–132 (1982).

    Article  CAS  Google Scholar 

  26. Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

    Article  ADS  CAS  Google Scholar 

  27. Chomczynski, P. & Sacchi, N. Analyt. Biochem. 162, 156–159 (1987).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gründemann, D., Gorboulev, V., Gambaryan, S. et al. Drug excretion mediated by a new prototype of polyspecific transporter. Nature 372, 549–552 (1994). https://doi.org/10.1038/372549a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/372549a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing