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Electrogenic uptake of nucleosides and nucleoside‐derived drugs by the human nucleoside transporter 1 (hCNT1) expressed in Xenopus laevis oocytes
Author(s) -
Lostao M.Pilar,
Mata Joao F.,
Larrayoz Ignacio M.,
Inzillo Simone M.,
Casado F.Javier,
Pastor-Anglada Marçal
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01983-9
Subject(s) - nucleoside transporter , nucleoside , cytidine , xenopus , uridine , biology , biochemistry , transporter , chemistry , rna , enzyme , gene
The concentrative pyrimidine‐preferring nucleoside transporter 1 (hCNT1), cloned from human fetal liver, was expressed in Xenopus laevis oocytes. Using the two‐electrode voltage‐clamp technique, it is shown that translocation of nucleosides by this transporter generates sodium inward currents. Membrane hyperpolarization (from −50 to −150 mV) did not affect the K 0.5 for uridine, although it increased the transport current approximately 3‐fold. Gemcitabine (a pyrimidine nucleoside‐derived drug) but not fludarabine (a purine nucleoside‐derived drug) induced currents in oocytes expressing the hCNT1 transporter. The K 0.5 value for gemcitabine at −50 mV membrane potential was lower than that for natural substrates, although this drug induced a lower current than uridine and cytidine, thus suggesting that the affinity binding of the drug transporter is high but that translocation occurs more slowly. The analysis of the currents generated by the hCNT1‐mediated transport of nucleoside‐derived drugs used in anticancer and antiviral therapies will be useful in the characterization of the pharmacological profile of this family of drug transporters and will allow rapid screening for uptake of newly developed nucleoside‐derived drugs.