Concentrative nucleoside transporter CNT

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... 

In addition to these transporters, specific transporters for hexoses (GLUT-1), amino acids (EAATl-3, LATl), and nucleosides (concentrative nucleoside transporters - CNT (SLC28 family) and equilibrative nucleoside transporters - ENT (SLC29 family) were reported as being present at the BBB. 

Nucleoside Transporter Families Concentrative Nucleoside Transporters (CNT, SLC28) and Equilihrative Nucleoside Transporters (ENT, SLC29)... 

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.

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). 

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)... 

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. 

Nucleoside analogues are widely used for the treatment of cancers and viral infections. Although there have been considerable advances in the development of new nucleoside analogs, little is known about the transport mechanisms involved in the intestinal absorption of these compounds. Nucleoside transporters have been subdivided into two major classes by Na+-independent equilibrative transporters (ENT family) and Na+-dependent concentrative transporters (CNT family) [77,100-103],... 

It is probable that CNT distribution is broader than expected due to the somehow specific role that these transporter proteins can play either in fine-tuning the extracellular adenosine concentration or in the need for a vectorial flux of nucleosides in particular tissue barriers. On the other hand, the complex pattern of NT expression, in general, does not rule out the possibility of actual redundancy, as must be the case probably in the ENTl-null mouse, as previously discussed. 

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