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Figure 1. Tranilast inhibits urate transport mediated by the human urate transporter URAT1 expressed in Xenopus laevis oocytes. (A) Time course of [14C]‐urate uptake by control and URAT1‐expressing oocytes. [14C]‐urate uptake by URAT1‐expressing oocytes was trans‐stimulated by preinjecting with 50 nL of 100 mmol/L PZA or nicotinate (Nico) 2 h before [14C]‐urate uptake experiment. Urate uptakes in the control oocytes were identical, resulting in superimposed data. Inset, western blot analysis of URAT1 protein expressed in oocytes. (B) [14C]‐urate transport properties of URAT1: voltage sensitivity and Na+‐dependence was examined by replacing extracellular NaCl by KCl or LiCl. Chloride effects were also examined; for the 0 Cl− bath, NaCl was replaced by Na‐gluconate (Na‐Gluc), KCl by K‐gluconate (K‐Gluc), MgCl2 by Mg‐gluconate, and CaCl2 by Ca‐gluconate. *P < 0.001 compared with NaCl (ND96). (C) Trans‐stimulatory effects of preloaded organic anions on [14C]‐urate uptake by URAT1‐expressing oocytes: [14C]‐urate uptake rate via URAT1 was measured in URAT1‐expressing oocytes preloaded with 50 nL of 100 mmol/L Lac, Nico, PZA, PAH, BHB or salicylate (Sal). *P < 0.001 compared with water‐injected control; NS, not significant. (D). Inhibition of [14C]urate by URAT1 in the presence of extracellular organic anions or uricosuric drugs, including tranilast: the uptake of [14C]‐urate (40 μmol/L) by URAT1‐expressing oocytes in exchange of preloaded intracellular nicotinate was determined after 1 h in the absence or presence of inhibitors (uricosuric drugs or organic anions) that were added to the extracellular medium (pH 7.4) at the indicated concentrations. *P < 0.001 compared with DMSO. Tran, Benz, Prob, DMSO. Data are mean ± S.E. with n = 12–15. (E) The 50% inhibitory concentration (IC 50) curve of tranilast for [14C]‐urate uptake‐mediated by URAT1 in oocytes preloaded with nicotinate. PZA, pyrazine carboxylate; PAH, para‐aminohippurate; Tran, tranilast; Benz, benzbromarone; Prob, probenecid; DMSO, dimethylsulfoxide. Image published in: Mandal AK et al. (2017) © 2017 The Authors. This image is reproduced with permission of the journal and the copyright holder. This is an open-access article distributed under the terms of the Creative Commons Attribution license Larger Image Printer Friendly View

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