Concentrative nucleoside transporter

Aymerich I, Duflot S, Fernandez-Veledo S, Guillen-Gomez E, Huber-Ruano I, Casado FJ, et al. The concentrative nucleoside transporter family (SLC28) new roles beyond salvage Biochem Soc Trans 2005 33 216-9. 

Figure 12.2 Adenosine metabolism. Intracellular adenosine concentrations depend on the balance between energy storage and breakdown. The most important enzymes catalyzing the reactions are indicated. SAH, S-adenosyl-homocysteine ENTs equilibrative nucleoside transporters CNTs, concentrating nucleoside transporters.

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. 

An increase of intracellular adenosine levels can also be achieved by inhibition of nucleoside transport proteins. Mammalian nucleoside transport processes can be classified into two types on the basis of their thermodynamic properties. These classes are the concentrative, Na+-dependent transport processes and the equilibrative, Na+-independent processes. The corresponding transporters are called CNTs (concentrative nucleoside transporters) and ENTs (equilibrative nucleoside transporters) (Pastor-Anglada and Baldwin, 2001). 

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. 

The brain needs the influx of nucleosides because the brain is deficient in de novo nucleotide synthesis (102). Purine and pyrimidine nucleosides are necessary for the synthesis of DNA and RNA, but nucleosides also influence many other biological processes. In addition, nucleosides play an important role in the treatment of diseases, such as cardiac diseases, brain cancers, and infections [parasitic and viral (103)]. Nucleosides are hydrophilic compounds, and the influx and efflux of these compounds is therefore mediated by a number of distinct transporters (104). Nucleoside transporters are membrane-fixed transporters and are classified by their transport mechanisms (e = equilibrative, c = concentrative), their sensitivity to the transport inhibitor nitrobenzylmercaptopurine riboside (NBMPR s = sensitive, i = insensitive), and their substrates. Presently, there are two equilibrative transporters (ENTs es and ei) and six concentrative nucleoside transporters [CNTs cif (concentrative, NBMPR insensitive, broad specificity Nl), cit (concentrative, NBMPR insensitive, common permeant thymidine N2), cib (concentrative, NBMPR insensitive, broad specificity N3), cib (concentrative, MBMPR insensitive, broad specificity N4), cs (concentrative, NBMPR sensitive N5), and csg (concentrative, NBMPR sensitive, accepts guanosine as permeant N6) (104)]. The equilibrative es and ei nucleoside transporters are widely expressed in mammalian cells and are present at cultured endothelial cells and brain capillaries (105). In these cells, the expression of concentrative transporter cit (N2) was demonstrated also. In other parts of the rat brain, ei and es nucleoside transport systems have... 

ABC ATP CDX CNT ENT EMT GIT GO NCE PEPT1 PMT QSAR SAR SLC ATP-binding cassette Adenosine 5 -triphosphate Caudal-type homeobox transcription factor Concentrative nucleoside transporter Equilibrative nucleoside transporter Epithelial-mesenchymal transition Gastrointestinal tract Gene ontology New chemical entity Di/tri-peptide transporter 1 Pharmacogenetics of Membrane Transporters Project Quantitative structure-activity relationship Structure-activity relationship Solute carriers (SLCs)... 

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,... 

M. (2001) Lipopolysaccharide-induced apoptosis of macrophages determines the up-regulation of concentrative nucleoside transporters Cntl and Cnt2 through tumor necrosis factor-alpha-dependent and -independent mechanisms. The Journal of Biological Chemistry, 276 (32), 30043-30049. 

Mangravite, L.M., Lipschutz, J.H., Mostov, K.E., and Giacomini, K.M. (2001) Localization of GFP-tagged concentrative nucleoside transporters in a renal polarized epithelial cell line. American Journal of Physiology. Renal Physiology,... 

Valdes. R.. Casado, F.J.. and Pastor-Anglada. M. (2002) Cell-cyde-dependent regulation of CNTl, a concentrative nucleoside transporter involved in the uptake of cell-cycle-dependent nucleoside-derived anticancer drugs. Biochemical and Biophysical Research Communications, 296 (3), 575-579. 

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. Journal of Hepatology, 41 (4), 538-544. 

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