TY - JOUR T1 - Rat Multispecific Organic Anion Transporter 1 (rOAT1) Transports Zidovudine, Acyclovir, and Other Antiviral Nucleoside Analogs JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 844 LP - 849 VL - 294 IS - 3 AU - Saiko Wada AU - Minoru Tsuda AU - Takashi Sekine AU - Seok Ho Cha AU - Miyako Kimura AU - Yoshikatsu Kanai AU - Hitoshi Endou Y1 - 2000/09/01 UR - http://jpet.aspetjournals.org/content/294/3/844.abstract N2 - Organic anion transporter 1 (OAT1) is ap-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 laevisoocytes. 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 μM, 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. The American Society for Pharmacology and Experimental Therapeutics ER -