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Gene Review

Slc28a1  -  solute carrier family 28 (concentrative...

Rattus norvegicus

Synonyms: CNT 1, Cnt1, Concentrative nucleoside transporter 1, Na(+)/nucleoside cotransporter 1, Sodium-coupled nucleoside transporter 1, ...
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Disease relevance of Slc28a1

  • Since such drugs are to some extent cell-cycle-dependent in their cytotoxic action, we examined the relationship between CNT1 expression and cell-cycle progression in the rat hepatoma cell line FAO [1].

High impact information on Slc28a1

  • BACKGROUND & AIMS: Concentrative nucleoside transporters CNT1 (pyrimidine preferring) and CNT2 (purine preferring) may be involved in the uptake of nucleoside-derived drugs used in antiviral and chemical therapies [2].
  • CNT1 was sensitive to nutrient availability in small intestine and, accordingly, jejunal brush border membrane vesicles from 48-hour-fasted rats showed increased expression of CNT1 and enhanced Na(+)-dependent thymidine and gemcitabine uptake [2].
  • CONCLUSIONS: Substrate availability modulates nucleoside transporter expression (CNT1) in rat jejunum in vivo [2].
  • METHODS: CNT1 and CNT2 tissue distribution was determined by Western blot analysis [2].
  • CNT1 was also absent in a cell line, L25, derived from the Alb-SV40 transgenic rat liver tumors, whereas another cell line, L37, derived from the normal-appearing parenchyma, retained the expression of both carrier isoforms [3].

Biological context of Slc28a1


Anatomical context of Slc28a1


Associations of Slc28a1 with chemical compounds

  • Low Na+-dependent uridine uptake was associated with low amounts of CNT1 and CNT2 transporter proteins, both with apparent Km values in the low micromolar range [7].
  • Expression of concentrative nucleoside transporters SLC28 (CNT1, CNT2, and CNT3) along the rat nephron: effect of diabetes [11].
  • When cells were synchronized using hydroxyurea (HU), which directly interacts with nucleotide metabolism by inhibiting ribonucleotide reductase, CNT1 protein amounts increased in synchronized cells and remained high during cell-cycle progression [1].
  • Functional characterization of a recombinant sodium-dependent nucleoside transporter with selectivity for pyrimidine nucleosides (cNT1rat) by transient expression in cultured mammalian cells [12].
  • Thus the stimulatory effect of NBTI on the concentrative nucleoside transporter of liver parenchymal cells cannot be explained by inhibition of nucleoside efflux [13].

Other interactions of Slc28a1

  • BACKGROUND: The renal reabsorption of natural nucleosides and a variety of nucleoside-derived drugs relies on the function of the apically located, Na(+)-dependent, concentrative nucleoside transporters CNT1, CNT2, and CNT3 (SLC28A1, SLC28A2, and SLC28A3) [11].
  • The Na+-dependent nucleoside transporter CNT1 has been identified in a caveolin-enriched plasma membrane fraction (CEF), in transcytotic endosomes, and in canalicular membranes isolated from quiescent rat liver in which the transporter appears to be biologically active [8].
  • Cnt1 transcripts were highest in small intestine, followed by kidney and testes, with similar expression in both species [14].
  • It is concluded that the recently characterized hepatic concentrative nucleoside transporter is under short-term hormonal regulation by glucagon, through mechanisms which involve membrane hyperpolarization, and under long-term control by insulin [15].

Analytical, diagnostic and therapeutic context of Slc28a1

  • Immunocytochemistry revealed that the CNT1 protein was indeed absent in the tumor lesions [3].
  • The cellular expression of equilibrative (ENT1, ENT2, ENT3) and concentrative (CNT1, CNT2, CNT3) NT subtypes was also determined using both qualitative and quantitative polymerase chain reaction techniques [16].
  • The production of recombinant cNT1rat was examined by immunoblotting using an epitope-tagged construct and by analysis of inward fluxes of 3H-labelled nucleosides [12].
  • Though CNT1 protein amounts increase in rat liver soon after partial hepatectomy, the physiological regulators of CNT1 expression have not yet been identified [10].


  1. Cell-cycle-dependent regulation of CNT1, a concentrative nucleoside transporter involved in the uptake of cell-cycle-dependent nucleoside-derived anticancer drugs. Valdés, R., Casado, F.J., Pastor-Anglada, M. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  2. Nutritional regulation of nucleoside transporter expression in rat small intestine. Valdés, R., Ortega, M.A., Casado, F.J., Felipe, A., Gil, A., Sánchez-Pozo, A., Pastor-Anglada, M. Gastroenterology (2000) [Pubmed]
  3. Selective loss of nucleoside carrier expression in rat hepatocarcinomas. Dragan, Y., Valdés, R., Gomez-Angelats, M., Felipe, A., Javier Casado, F., Pitot, H., Pastor-Anglada, M. Hepatology (2000) [Pubmed]
  4. Cloned blood-brain barrier adenosine transporter is identical to the rat concentrative Na+ nucleoside cotransporter CNT2. Li, J.Y., Boado, R.J., Pardridge, W.M. J. Cereb. Blood Flow Metab. (2001) [Pubmed]
  5. Na+ reabsorption in cultured rat epididymal epithelium via the Na+/nucleoside cotransporter. Leung, G.P., Cheung, K.H., Tse, C.M., Wong, P.Y. Biol. Reprod. (2001) [Pubmed]
  6. Sorting of rat SPNT in renal epithelium is independent of N-glycosylation. Mangravite, L.M., Giacomini, K.M. Pharm. Res. (2003) [Pubmed]
  7. Developmental regulation of the concentrative nucleoside transporters CNT1 and CNT2 in rat liver. del Santo, B., Tarafa, G., Felipe, A., Casado, F.J., Pastor-Anglada, M. J. Hepatol. (2001) [Pubmed]
  8. Concentrative nucleoside transporter (rCNT1) is targeted to the apical membrane through the hepatic transcytotic pathway. Duflot, S., Calvo, M., Casado, F.J., Enrich, C., Pastor-Anglada, M. Exp. Cell Res. (2002) [Pubmed]
  9. Transport mechanisms for adenosine and uridine in primary-cultured rat cortical neurons and astrocytes. Nagai, K., Nagasawa, K., Fujimoto, S. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  10. Up-regulation of the high-affinity pyrimidine-preferring nucleoside transporter concentrative nucleoside transporter 1 by tumor necrosis factor-alpha and interleukin-6 in liver parenchymal cells. Fernández-Veledo, S., Valdés, R., Wallenius, V., Casado, F.J., Pastor-Anglada, M. J. Hepatol. (2004) [Pubmed]
  11. Expression of concentrative nucleoside transporters SLC28 (CNT1, CNT2, and CNT3) along the rat nephron: effect of diabetes. Rodríguez-Mulero, S., Errasti-Murugarren, E., Ballarín, J., Felipe, A., Doucet, A., Casado, F.J., Pastor-Anglada, M. Kidney Int. (2005) [Pubmed]
  12. Functional characterization of a recombinant sodium-dependent nucleoside transporter with selectivity for pyrimidine nucleosides (cNT1rat) by transient expression in cultured mammalian cells. Fang, X., Parkinson, F.E., Mowles, D.A., Young, J.D., Cass, C.E. Biochem. J. (1996) [Pubmed]
  13. Nucleoside uptake in rat liver parenchymal cells. Mercader, J., Gomez-Angelats, M., del Santo, B., Casado, F.J., Felipe, A., Pastor-Anglada, M. Biochem. J. (1996) [Pubmed]
  14. Tissue distribution of concentrative and equilibrative nucleoside transporters in male and female rats and mice. Lu, H., Chen, C., Klaassen, C. Drug Metab. Dispos. (2004) [Pubmed]
  15. Hormonal regulation of concentrative nucleoside transport in liver parenchymal cells. Gomez-Angelats, M., del Santo, B., Mercader, J., Ferrer-Martinez, A., Felipe, A., Casado, J., Pastor-Anglada, M. Biochem. J. (1996) [Pubmed]
  16. Nucleoside transporter subtype expression and function in rat skeletal muscle microvascular endothelial cells. Archer, R.G., Pitelka, V., Hammond, J.R. Br. J. Pharmacol. (2004) [Pubmed]
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