Skip to main content
Log in

Functional and Molecular Characteristics of Na+-dependent Nucleoside Transporters

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Nucleoside transporters play a critical role in the absorption, disposition, and targeting of therapeutically used nucleosides and nucleoside analogs. This review is focused on the Na+-dependent, concentrative nucleoside transporters which are found in a variety of cells including renal, intestinal and hepatic epithelia. Five major Na+-dependent nucleoside transporter subtypes have been characterized in isolated tissue preparations: Nl is purine selective; N2 is pyrimidine selective and N3−N5 exhibit variable selectivity for both purine and pyrimidine nucleosides. The recent cloning of Nl and N2 nucleoside transporters has provided the first information on the molecular function and structure of concentrative nucleoside transporters. In this manuscript we review the characteristics of the various subtypes of nucleoside transporters and the molecular structure, functional properties, and tissue distribution of the cloned Na+-dependent nucleoside transporters. In addition, the interactions of nucleosides and nucleoside analogs with the cloned transporters in mammalian and amphibian expression systems are presented. Mammalian expression systems may be particularly useful during drug development in screening potential compounds for improved bioavailability and tissue specific targeting. Finally, we present our view of future areas of study in the field of nucleoside transporters.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. B. A. Larder, A. Kohli, S. Bloor, S. D. Kemp, P. R. Harrigan, R. T. Schooley, J. M. Lange, K. N. Pennington, and M. H. St. Clair. J Virol 70:5922–9, 1996.

    Google Scholar 

  2. A. Saven, M. L. Figueroa, L. D. Piro, and J. D. Rosenblatt. N Engl J Med 329:734–5, 1993.

    Google Scholar 

  3. A. Saven and L. D. Piro. Cancer 72:3470–83, 1993.

    Google Scholar 

  4. T. Hickish, P. Serafinowski, D. Cunningham, A. Oza, E. Dorland, I. Judson, B. C. Millar, T. A. Lister, and A. Roldan. Br J Cancer 67:139–43, 1993.

    Google Scholar 

  5. W. J. Brady Jr., D. J. DeBehnke, L. L. Wickman, and G. Lindbeck. Acad Emerg Med 3:574–85, 1996.

    Google Scholar 

  6. L. Belardinelli, J. Linden, and R. M. Berne. Prog Cardiovasc Dis 32:73–97, 1989.

    Google Scholar 

  7. T. Paul and J. P. Pfammatter. Pediatr Cardiol 18:118–26, 1997.

    Google Scholar 

  8. A. L. Tucker and J. Linden. Cardiovasc Res 27:62–7, 1993.

    Google Scholar 

  9. H. E. Dahlig, Y. Eilam, A. R. Paterson, and C. E. Cass. Biochem J 200:295–305, 1981.

    Google Scholar 

  10. M. Griffiths, N. Beaumont, S. Y. Yao, M. Sundaram, C. E. Boumah, A. Davies, F. Y. Kwong, I. Coe, C. E. Cass, and J. D. Young. Nat Med 3:89–93, 1997.

    Google Scholar 

  11. F. Y. Kwong, H. E. Fincham, A. Davies, N. Beaumont, P. J. Henderson, J. D. Young, and S. A. Baldwin. J Biol Chem 267:21954–60, 1992.

    Google Scholar 

  12. L. F. Barros, D. L. Yudilevich, S. M. Jarvis, N. Beaumont, J. D. Young, and S. A. Baldwin. Pflugers Arch 429:394–9, 1995.

    Google Scholar 

  13. J. Pressacco, J. S. Wiley, G. P. Jamieson, C. Erlichman, and D. W. Hedley. Br J Cancer 72:939–42, 1995.

    Google Scholar 

  14. P. G. Plagemann and J. M. Aran. Biochim Biophys Acta 1025:32–42, 1990.

    Google Scholar 

  15. M. M. Gutierrez, C. M. Brett, R. J. Ott, A. C. Hui, and K. M. Giacomini. Biochim Biophys Acta 1105:1–9, 1992.

    Google Scholar 

  16. J. A. Belt, N. M. Marina, D. A. Phelps, and C. R. Crawford. Adv Enzyme Regul 33:235–52, 1993.

    Google Scholar 

  17. X. Wu, G. Yuan, C. M. Brett, A. C. Hui, and K. M. Giacomini. J Biol Chem 267:8813–8, 1992.

    Google Scholar 

  18. D. A. Griffith and S. M. Jarvis. Biochim Biophys Acta 1286:153–81, 1996.

    Google Scholar 

  19. C. E. Cass. Nucleoside transport, in Drug Transport in Antimicrobial and Anticancer Chemotherapy. (N. H. Georgopapadakou, ed.). Marcel Dekker, New York 403–451, 1995.

    Google Scholar 

  20. C. W. Lee, C. I. Cheeseman, and S. M. Jarvis. Am J Physiol F1203–10, 1990.

  21. C. R. Crawford, C. Y. Ng, and J. A. Belt. J Biol Chem 265:13730–4, 1990.

    Google Scholar 

  22. D. Vijayalakshmi and J. A. Belt. Two transport systems with differing substrate specificities. J Biol Chem 263:19419–23, 1988.

    Google Scholar 

  23. K. I. Roovers and K. A. Meckling-Gill. J Cell Physiol 166:593–600, 1996.

    Google Scholar 

  24. Q. Q. Huang, C. M. Harvey, A. R. Paterson, C. E. Cass, and J. D. Young. J Biol Chem 268:20613–9, 1993.

    Google Scholar 

  25. X. Wu, M. M. Gutierrez, and K. M. Giacomini. Biochim Biophys Acta 1191:190–6, 1994.

    Google Scholar 

  26. M. J. Redlak, Z. E. Zehner, and S. L. Betcher. Biochem Biophys Res Commun 225:106–11, 1996.

    Google Scholar 

  27. M. M. Gutierrez and K. M. Giacomini. Biochim Biophys Acta 1149:202–8, 1993.

    Google Scholar 

  28. Q. Q. Huang, S. Y. Yao, M. W. Ritzel, A. R. Paterson, C. E. Cass, and J. D. Young. J Biol Chem 269:17757–60, 1994.

    Google Scholar 

  29. M. Che, D. F. Ortiz, and I. M. Arias. J Biol Chem 270:13596–9, 1995.

    Google Scholar 

  30. M. W. Ritzel, S. Y. Yao, M. Y. Huang, J. F. Elliott, C. E. Cass, and J. D. Young. Am J Physiol 272:C707–C714, 1997.

    Google Scholar 

  31. J. Wang, S. F. Su, M. J. Dresser, M. E. Schaner, C. B. Washington, and K. M. Giacomini. Am J Physiol (in press), 1997.

  32. D. Grundemann, V. Gorboulev, S. Gambaryan, M. Veyhl, and H. Koepsell. Nature 372:549–52, 1994.

    Google Scholar 

  33. M. A. Hediger, M. J. Coady, T. S. Ikeda, and E. M. Wright Nature 330:379–81, 1987.

    Google Scholar 

  34. R. M. Wohlhueter and P. G. Plagemann. Int Rev Cytol 64:171–240, 1980.

    Google Scholar 

  35. H. C. Wang, B. Beer, D. Sassano, A. J. Blume, and M. R. Ziai. Int J Biochem 23:271–6, 1991.

    Google Scholar 

  36. S. M. Jarvis and D. A. Griffith. Biochem J 605–7, 1991.

  37. S. Y. Yao, A. M. Ng, M. W. Ritzel, W. P. Gati, C. E. Cass C. E., and J. D. Young. Mol Pharmacol 50:1529–35, 1996.

    Google Scholar 

  38. S. Y. Yao, C. E. Cass, and J. D. Young. Mol Pharmacol 50:388–93, 1996.

    Google Scholar 

  39. X. Fang, F. E. Parkinson, D. A. Mowles, J. D. Young, and C. E. Cass. Biochem J 457–65, 1996.

  40. M. E. Schaner, J. Wang, S. Zevin, K. M. Gerstin, and K. M. Giacomini. Pharm Res (in press), 1997.

  41. C. M. Anderson, W. Xiong, J. D. Young, C. E. Cass, and F. E. Parkinson. Brain Res Mol Brain Res 42:358–61, 1996.

    Google Scholar 

  42. G. Chandrasena, S. Patil, R. Giltay, A. Bakken, and J. D. Unadkat. Pharm. Res. 13:S-410 (Abstr.), 1996.

    Google Scholar 

  43. A. M. Pajor and E. M. Wright. J Biol Chem 267:3557–60, 1992.

    Google Scholar 

  44. M. Le Hir. Renal Physiol. Biochem. 13:154–161, 1990.

    Google Scholar 

  45. B. B. Lerman and L. Belardinelli. Circulation 83:1499–1509, 1991.

    Google Scholar 

  46. I. Patsan, M. C. Willingham, and M. Gottesman. FASEB J. 5:2523–2528, 1991.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kathleen M. Giacomini.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, J., Schaner, M.E., Thomassen, S. et al. Functional and Molecular Characteristics of Na+-dependent Nucleoside Transporters. Pharm Res 14, 1524–1532 (1997). https://doi.org/10.1023/A:1012113931332

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1012113931332

Navigation