2007
DOI: 10.1113/jphysiol.2007.130138
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Abstract: We examined the role of the concentrative nucleoside transporter CNT3 in the establishment of a transepithelial flux of natural nucleosides and their pharmacologically active derivatives in renal epithelial cell lines. Murine PCT cells grown on a transwell dish showed endogenous CNT3 activity at their apical membrane that was responsible for the sodium-dependent transepithelial flux of both purine and pyrimidine nucleosides. hCNT3 was also identified in human kidney and its role in the transport of nucleosides… Show more

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Cited by 58 publications
(75 citation statements)
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“…CNT3 has also been shown to transport gemcitabine and the antiviral drugs azidothymidine and ribavirin (Hu et al, 2006;Yamamoto et al, 2007). Its location at the apical membrane of a polarized cell model (Mangravite et al, 2003;Errasti-Murugarren et al, 2007) together with its presence along the rat and human renal tubule (Rodríguez-Mulero et al, 2005;Damaraju et al, 2007) and human intestine (Ritzel et al, 2001) suggest that CNT3 plays an important role in the absorption and disposition of nucleosides and synthetic nucleoside analogs.…”
mentioning
confidence: 99%
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“…CNT3 has also been shown to transport gemcitabine and the antiviral drugs azidothymidine and ribavirin (Hu et al, 2006;Yamamoto et al, 2007). Its location at the apical membrane of a polarized cell model (Mangravite et al, 2003;Errasti-Murugarren et al, 2007) together with its presence along the rat and human renal tubule (Rodríguez-Mulero et al, 2005;Damaraju et al, 2007) and human intestine (Ritzel et al, 2001) suggest that CNT3 plays an important role in the absorption and disposition of nucleosides and synthetic nucleoside analogs.…”
mentioning
confidence: 99%
“…There are two families of nucleoside carriers in mammalian cells, the equilibrative ENT/SLC29A transporters, with low affinity and wide selectivity, and the concentrative CNT/SLC28A transporters, with higher affinity and more restricted selectivity (Griffith and Jarvis, 1996;Baldwin et al, 1999). Because absorptive cells in the renal and intestinal epithelia express all members of the concentrative CNT family (Gutierrez and Giacomini, 1993;Ngo et al, 2001;Rodríguez-Mulero et al, 2005;Errasti-Murugarren et al, 2007), any change in their activity might be highly relevant in the pharmacokinetics of nucleoside-derived drugs.…”
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confidence: 99%
“…Numerous studies have linked nucleoside analog chemotherapy drug resistance to decreased nucleoside transporter expression (18,20,45). ENT1 is generally accepted as the primary RBV transporter; however, CNT2, CNT3, and ENT2 may also transport RBV in various cell types (13,28,39,51). Our previous work determined that ENT1 was the primary RBV transporter in Huh7 liver cells.…”
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confidence: 99%
“…As such, we describe here for the first time an in vitro cell model for measurements of the vectorial transport of nucleosides and nucleoside analogs by unidirectional transport proteins from the apical to the basolateral membrane. A recent study reported that a single-transfected MDCK cell line expressing recombinant hCNT3 in the apical membrane showed increased apical-to-basolateral transport of cytidine (Errasti-Murugarren et al, 2007). However, the efflux transporters in the basolateral membrane of the cells were of endogenous origin.…”
Section: Discussionmentioning
confidence: 99%
“…As a nucleoside uptake transporter for this cell model, we selected hCNT3 because it transports purine and pyrimidine nucleosides and various therapeutic nucleoside analogs in a concentrative manner and with a broad substrate specificity (Ritzel et al, 2001;Sarkar et al, 2005;Errasti-Murugarren et al, 2007). In addition, hCNT3 seems to concentrate nucleosides intracellularly more efficiently than hCNT1 or hCNT2; thus, it is expected to play an important role in the pharmacokinetics of nucleoside analogs (Mangravite et al, 2003).…”
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confidence: 99%