Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs.
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Wada S, Tsuda M, Sekine T, Cha SH, Kimura M, Kanai Y, Endou H
Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs.
J Pharmacol Exp Ther. 2000 Sep;294(3):844-9.
- PubMed ID
- 10945832 [ View in PubMed]
- Abstract
Organic anion transporter 1 (OAT1) is a p-aminohippurate/dicarboxylate exchanger that plays a primary role in the tubular secretion of endogenous and exogenous organic anions. OAT1 is located in the basolateral membrane of the proximal tubular cells and mediates the uptake of various organic anions from the peritubular fluid. In this study, we investigated the transport of antiviral nucleoside analogs via rat OAT1 (rOAT1) using a heterologous expression system in Xenopus laevis oocytes. Oocytes injected with rOAT1 cRNA showed significantly higher uptake of zidovudine (AZT) and acyclovir (ACV) than control oocytes. rOAT1-mediated uptake of AZT and ACV was probenecid-sensitive and increased by the outwardly directed gradient of glutarate. The affinity of rOAT1 for AZT and ACV was determined to be 68 and 242 microM, respectively. Five other antiviral agents that we studied (zalcitabine, didanosine, lamivudine, stavudine, and trifluridine) were also shown to be transported by rOAT1, whereas foscarnet, a phosphate analog, was not. The aforementioned nucleoside analogs lack a typical anionic group and are not very hydrophobic. This study demonstrates extension of the substrate spectrum of rOAT1 and provides a molecular basis for the pharmacokinetics of antiviral nucleoside analogs.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Acyclovir Solute carrier family 22 member 6 Protein Humans UnknownSubstrateInhibitorDetails Didanosine Solute carrier family 22 member 6 Protein Humans UnknownSubstrateDetails Foscarnet Solute carrier family 22 member 6 Protein Humans UnknownInhibitorDetails Lamivudine Solute carrier family 22 member 6 Protein Humans UnknownSubstrateDetails Stavudine Solute carrier family 22 member 6 Protein Humans UnknownSubstrateDetails Trifluridine Solute carrier family 22 member 6 Protein Humans UnknownSubstrateInhibitorDetails Valaciclovir Solute carrier family 22 member 6 Protein Humans UnknownNot Available Details Zalcitabine Solute carrier family 22 member 6 Protein Humans UnknownSubstrateDetails