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Figure 3. Tranilast inhibits urate transport mediated by the human urate/dicarboxylate exchanger OAT4. (A) The uptake of [14C]‐urate by OAT4‐expressing oocytes was performed in ND96 medium (pH 7.4) at ~25°C for 1 h. Na+‐dependence was examined by replacing extracellular NaCl by KCl. The [14C]‐urate uptake by OAT4‐expressing oocytes was found to be significantly trans‐stimulated when OAT4‐expressing oocytes were preinjected with 50 nL of 100 mmol/L maleate (Mal); preinjection with 50 nL of 100 mmol/L succinate (Succi), α‐ketogluterate (α‐KG), nicotinate (Nico), or PZA had no significant effects. Asterisk, P < 0.001 compared with water‐injected control. (B) The inhibition of [14C]‐urate uptake by OAT4 was examined in the presence of extracellular organic anions (for cis‐inhibition) or uricosuric drugs at the indicated concentrations. Asterisk, P < 0.001 compared with DMSO/NaCl(ND96). Tran, Benz, Prob, DMSO. Data are mean ± S.E. with n = 12–15. PZA, pyrazine carboxylate; Tran, Tranilast; Benz, Benzbromarone; Prob, probenecid; DMSO, dimethylsulfoxide; Lac, lactate; Nico, nicotinate. 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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