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.
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REFERENCES
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.
A. Saven, M. L. Figueroa, L. D. Piro, and J. D. Rosenblatt. N Engl J Med 329:734–5, 1993.
A. Saven and L. D. Piro. Cancer 72:3470–83, 1993.
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.
W. J. Brady Jr., D. J. DeBehnke, L. L. Wickman, and G. Lindbeck. Acad Emerg Med 3:574–85, 1996.
L. Belardinelli, J. Linden, and R. M. Berne. Prog Cardiovasc Dis 32:73–97, 1989.
T. Paul and J. P. Pfammatter. Pediatr Cardiol 18:118–26, 1997.
A. L. Tucker and J. Linden. Cardiovasc Res 27:62–7, 1993.
H. E. Dahlig, Y. Eilam, A. R. Paterson, and C. E. Cass. Biochem J 200:295–305, 1981.
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.
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.
L. F. Barros, D. L. Yudilevich, S. M. Jarvis, N. Beaumont, J. D. Young, and S. A. Baldwin. Pflugers Arch 429:394–9, 1995.
J. Pressacco, J. S. Wiley, G. P. Jamieson, C. Erlichman, and D. W. Hedley. Br J Cancer 72:939–42, 1995.
P. G. Plagemann and J. M. Aran. Biochim Biophys Acta 1025:32–42, 1990.
M. M. Gutierrez, C. M. Brett, R. J. Ott, A. C. Hui, and K. M. Giacomini. Biochim Biophys Acta 1105:1–9, 1992.
J. A. Belt, N. M. Marina, D. A. Phelps, and C. R. Crawford. Adv Enzyme Regul 33:235–52, 1993.
X. Wu, G. Yuan, C. M. Brett, A. C. Hui, and K. M. Giacomini. J Biol Chem 267:8813–8, 1992.
D. A. Griffith and S. M. Jarvis. Biochim Biophys Acta 1286:153–81, 1996.
C. E. Cass. Nucleoside transport, in Drug Transport in Antimicrobial and Anticancer Chemotherapy. (N. H. Georgopapadakou, ed.). Marcel Dekker, New York 403–451, 1995.
C. W. Lee, C. I. Cheeseman, and S. M. Jarvis. Am J Physiol F1203–10, 1990.
C. R. Crawford, C. Y. Ng, and J. A. Belt. J Biol Chem 265:13730–4, 1990.
D. Vijayalakshmi and J. A. Belt. Two transport systems with differing substrate specificities. J Biol Chem 263:19419–23, 1988.
K. I. Roovers and K. A. Meckling-Gill. J Cell Physiol 166:593–600, 1996.
Q. Q. Huang, C. M. Harvey, A. R. Paterson, C. E. Cass, and J. D. Young. J Biol Chem 268:20613–9, 1993.
X. Wu, M. M. Gutierrez, and K. M. Giacomini. Biochim Biophys Acta 1191:190–6, 1994.
M. J. Redlak, Z. E. Zehner, and S. L. Betcher. Biochem Biophys Res Commun 225:106–11, 1996.
M. M. Gutierrez and K. M. Giacomini. Biochim Biophys Acta 1149:202–8, 1993.
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.
M. Che, D. F. Ortiz, and I. M. Arias. J Biol Chem 270:13596–9, 1995.
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.
J. Wang, S. F. Su, M. J. Dresser, M. E. Schaner, C. B. Washington, and K. M. Giacomini. Am J Physiol (in press), 1997.
D. Grundemann, V. Gorboulev, S. Gambaryan, M. Veyhl, and H. Koepsell. Nature 372:549–52, 1994.
M. A. Hediger, M. J. Coady, T. S. Ikeda, and E. M. Wright Nature 330:379–81, 1987.
R. M. Wohlhueter and P. G. Plagemann. Int Rev Cytol 64:171–240, 1980.
H. C. Wang, B. Beer, D. Sassano, A. J. Blume, and M. R. Ziai. Int J Biochem 23:271–6, 1991.
S. M. Jarvis and D. A. Griffith. Biochem J 605–7, 1991.
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.
S. Y. Yao, C. E. Cass, and J. D. Young. Mol Pharmacol 50:388–93, 1996.
X. Fang, F. E. Parkinson, D. A. Mowles, J. D. Young, and C. E. Cass. Biochem J 457–65, 1996.
M. E. Schaner, J. Wang, S. Zevin, K. M. Gerstin, and K. M. Giacomini. Pharm Res (in press), 1997.
C. M. Anderson, W. Xiong, J. D. Young, C. E. Cass, and F. E. Parkinson. Brain Res Mol Brain Res 42:358–61, 1996.
G. Chandrasena, S. Patil, R. Giltay, A. Bakken, and J. D. Unadkat. Pharm. Res. 13:S-410 (Abstr.), 1996.
A. M. Pajor and E. M. Wright. J Biol Chem 267:3557–60, 1992.
M. Le Hir. Renal Physiol. Biochem. 13:154–161, 1990.
B. B. Lerman and L. Belardinelli. Circulation 83:1499–1509, 1991.
I. Patsan, M. C. Willingham, and M. Gottesman. FASEB J. 5:2523–2528, 1991.
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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
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DOI: https://doi.org/10.1023/A:1012113931332