Human concentrative nucleoside transporter

Mata, J. F., et al. Role of the human concentrative nucleoside transporter (hCNTl) in the cytotoxic action of 5[Prime]-deoxy-5-fluorouridine, an active intermediate metabolite of capecitabine, a novel oral anticancer drug. Mol. Pharmacol. 2001, 59, 1542— 1548. 

Lang, T.T., Seiner, M., Young, J.D., and Cass, C.E. (2001) Acquisition of human concentrative nucleoside transporter 2 (hcnt2) activity by gene transfer confers sensitivity to fluoropyrimidine nucleosides in drug-resistant leukemia cells. Molecular Pharmacology, 60 (5), 1143-1152. 

Toan SV, To KK, Leung GP, de Souza MO, Ward JL, Tse CM (2003) Genomic organization and functional characterization of the human concentrative nucleoside transporter-3 isoform (hCNT3) expressed in mammalian cells. Pfiigers Arch 447 195... 

Gray JH, Mangravite LM, Owen RP, Urban TJ, Chan W, Carlson EJ et al. Eunctional and genetic diversity in the concentrative nucleoside transporter, CNTl, in human populations. Mol Pharmacol 2004 65 512-9. 

Huang, C.C., Kawamoto, M., Johns, S.J., Stryke, D. et al. (2004) Functional and genetic diversity in the concentrative nucleoside transporter, CNT1, in human populations. Molecular Pharmacology,... 

Fig.n.2. Human duodenal expression variability of nucleoside, organic cation ion, and anion transporters (unpublished data). Shaded box indicates 25-75% of expression range, the line within the box marks the median, and error bars indicate 10-90% of expression range. ENT2, equilibrative nucleoside transporter CNT1, concentrative pyrimidine nucleoside transporter CNT2, concentrative purine nucleoside transporter ... 

The experiment in Figure 13-3 illustrates the use of flow cytometry to determine Kj and B ax values for binding of the es nucleoside transporter ligand, SAENTA-fiuorescein, at sites in human CEM leukemic lymphoblasts. The es nucleoside transporter is widely expressed in mammalian cells, and is concentrated in regions in the CNS that coordinately express adenosine Ai receptors (Jennings et al., 2001). 

While the PRTases salvage nucleobases within cells, nucleosides such as adenosine and uridine are present in the blood at much higher concentrations ( 1 pM) than the equivalent nucleobases, adenine and uracil. Indeed, the brain synthesizes pyrimidine nucleotides (UTP and CTP) via salvage synthesis from uridine produced by the liver and released into the circulation. Human cells may contain at least three types of nonspecific nucleoside transporters, and nucleosides are internalized more rapidly than nucleobases. 

Ritzel, M.W., Ng, A.M., Yao, S.Y., Graham, K., Loewen, S.K., Smith, K.M., Hyde, R.J., Karpinski, E., Cass, C.E., Baldwin, S.A., et al. (2001) Recent molecular advances in studies of the concentrative Na + -dependent nucleoside transporter (CNT) family identification and characterization of novel human and mouse proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib). Molecular Membrane Biology, 18 (1), 65-72. 

The use of radiolabeled nucleosides, taken up into proliferating cells and incorporated into DNA, is a well-known approach for the determination of cell proliferation, e.g., utilizing [ H] thymidine or fluorinated compounds (Shields et al. 1996). Nucleosides are taken up into cells by facilitated diffusion controlled by equilibrative and concentrative transporters. From the two groups of equilibrative transporters (es and is), the es-transporter is mainly expressed in human cell lines investigated so far. 

---