Biochemistry, Physiology, and Pharmacology of Nucleoside and Nucleobase Transporters

Pastor‐Anglada, Marçal; Molina‐Arcas, Míriam; Cano-Soldado, Pedro; Casado, F. Javier

doi:10.1002/9783527627424.ch2

Cited by 1 publication

(3 citation statements)

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“…The human ENT proteins (hENTs) family contain four members, hENT1-4 ( Molina-Arcas et al, 2009 ; Pastor-Anglada et al, 2009 ; Cano-Soldado and Pastor-Anglada, 2012 ; Molina-Arcas and Pastor-Anglada, 2013 ). hENTs, except hENT4, mediate the facilitative transport of natural nucleosides with broad selectivity but relatively lower affinity than their CNT-type counterparts ( Baldwin et al, 2004 ; Young et al, 2008 ).…”

Section: Nucleoside-derived Drug Transportersmentioning

confidence: 99%

“…Most cells express several NT-encoding genes, thereby anticipating some sort of apparent functional redundancy when analyzing transporter profiles, particularly considering that transporters often show overlapping or even identical selectivity profiles. Indeed, hCNT expression is commonly associated with fully differentiated cell types ( Molina-Arcas et al, 2009 ; Pastor-Anglada et al, 2009 ; Cano-Soldado and Pastor-Anglada, 2012 ; Molina-Arcas and Pastor-Anglada, 2013 ) and oncogenesis often results in hCNT down-regulation, particularly in hCNT1 ( Farre et al, 2004 ; Zollner et al, 2005 ; Lane et al, 2010 ; Bhutia et al, 2011 ; Martinez-Becerra et al, 2012 ; Mohelnikova-Duchonova et al, 2013 ; Table 4 ). However, the evidence of hCNT1 loss during oncogenesis needs further investigation, because almost all the studies performed so far focused exclusively on hCNT1-related mRNA levels.…”

Section: Nts As Drug Targetsmentioning

confidence: 99%

“…Nucleoside transporters (NTs) are integral membrane proteins implicated in the salvage of natural nucleobases and nucleosides for nucleic acid synthesis. NTs belong to solute carrier families 28 and 29 (SLC28 and SLC29), which encode human concentrative nucleoside transporters (hCNT) and equilibrative nucleoside transporter proteins (hENTs), respectively ( Molina-Arcas et al, 2009 ; Pastor-Anglada et al, 2009 ; Cano-Soldado and Pastor-Anglada, 2012 ; Molina-Arcas and Pastor-Anglada, 2013 ). However, the chemical modifications of the nucleoside analogs can alter their ability to interact with canonical transporter proteins implicated in the uptake of natural nucleosides.…”

mentioning

confidence: 99%

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Nucleoside transporter proteins as biomarkers of drug responsiveness and drug targets

Pastor‐Anglada

Pérez-Torras

2015

Front. Pharmacol.

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Nucleoside and nucleobase analogs are currently used in the treatment of solid tumors, lymphoproliferative diseases, viral infections such as hepatitis and AIDS, and some inflammatory diseases such as Crohn. Two gene families are implicated in the uptake of nucleosides and nucleoside analogs into cells, SCL28 and SLC29. The former encodes hCNT1, hCNT2, and hCNT3 proteins. They translocate nucleosides in a Na+ coupled manner with high affinity and some substrate selectivity, being hCNT1 and hCNT2 pyrimidine- and purine-preferring, respectively, and hCNT3 a broad selectivity transporter. SLC29 genes encode four members, being hENT1 and hENT2 the only two which are unequivocally implicated in the translocation of nucleosides and nucleobases (the latter mostly via hENT2) at the cell plasma membrane. Some nucleoside-derived drugs can also interact with and be translocated by members of the SLC22 gene family, particularly hOCT and hOAT proteins. Inter-individual differences in transporter function and perhaps, more importantly, altered expression associated with the disease itself might modulate the transporter profile of target cells, thereby determining drug bioavailability and action. Drug transporter pharmacology has been periodically reviewed. Thus, with this contribution we aim at providing a state-of-the-art overview of the clinical evidence generated so far supporting the concept that these membrane proteins can indeed be biomarkers suitable for diagnosis and/or prognosis. Last but not least, some of these transporter proteins can also be envisaged as drug targets, as long as they can show “transceptor” functions, in some cases related to their role as modulators of extracellular adenosine levels, thereby providing a functional link between P1 receptors and transporters.

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