title: Cell entry and export of nucleoside analogues.
abstract: Some nucleoside analogues currently used as antiretroviral agents might promote mutagenesis besides their putative ability to interfere with endogenous nucleotide metabolism and/or inhibit viral transcription. The intracellular concentration of nucleosides and nucleobases is to some extent the result of the metabolic background of the specific cell line used for infection studies, its particular suit of enzymes and transporters. This review focuses on the transporter-mediated pathways implicated in either the uptake or the efflux of nucleoside- and nucleobase-derivatives. From a biochemical point of view, four different types of transport processes for nucleoside-related antiviral drugs have been described: (1) equilibrative uniport, (2) substrate exchange, (3) concentrative Na+- or H+-dependent uptake and finally, (4) substrate export through primary ATP-dependent active efflux pumps. These mechanisms are mainly related to the following set of transporter families: Concentrative Nucleoside Transporter (CNT), Equilibrative Nucleoside Transporter (ENT), Organic Anion Transporter (OAT) and Organic Cation Transporter (OCT), Peptide Transporter (PEPT) and Multidrug Resistance Protein (MRP). The basic properties of these carrier proteins and their respective role in the transport across the plasma membrane of nucleoside-derived antiviral drugs are reviewed.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain. mpastor@ub.edu
authors.forename: Marçal
authors.initials: M
authors.lastname: Pastor-Anglada
authors.forename: Pedro
authors.initials: P
authors.lastname: Cano-Soldado
authors.forename: Míriam
authors.initials: M
authors.lastname: Molina-Arcas
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Lostao
authors.forename: Ignacio
authors.initials: I
authors.lastname: Larráyoz
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez-Picado
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Casado
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D033703:Nucleoside Transport Proteins / Q000378:metabolism*; D009705:Nucleosides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D012328:RNA Viruses / Q000187:drug effects / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D033703:Nucleoside Transport Proteins; D009705:Nucleosides