Figure 7.

Functional and pharmacological characterization of human nicotinate transporters, hSMCT1, SMCT2, and OAT10. The uptake of [¹⁴C]‐nicotinate (40 μmol/L) by SMCT1‐, SMCT2‐ or OAT10‐expressing oocytes was performed in ND96 medium (pH 7.4) at ~25°C. [¹⁴C]‐nicotinate transport properties of nicotinate transporters: voltage sensitivity and Na⁺‐dependence was examined by replacing extracellular NaCl by KCl or LiCl. Chloride ion‐dependence was also assessed; in 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. (A) [¹⁴C]‐nicotinate transport properties of human SMCT1 (B) [¹⁴C]nicotinate transport properties of human SMCT2. *P < 0.001 compared with NaCl (ND96). (C) Inhibition of [¹⁴C]‐nicotinate uptake via SMCT1, and SMCT2 in the presence of uricosuric drugs added into the extracellular medium (pH 7.4) at the indicated concentrations. P < 0.01 compared with NaCl (ND96); NS, not significant. (D) [¹⁴C]‐nicotinate transport properties of human OAT10 in oocytes preloaded with PZA. *P < 0.001 compared with uptake in the absence of inhibitor; NS, not significant. (E) Inhibition of [¹⁴C]‐nicotinate uptake via OAT10 (preloaded with PZA) in the presence of uricosuric drugs added into the extracellular medium (pH 7.4) at the indicated concentrations. P < 0.01 compared with NaCl (ND96); NS, not significant. Tran, Benz, Prob, DMSO. Data are mean ± S.E. with n = 12–15. PZA, pyrazine carboxylate; Tran, Tranilast; Benz, Benzbromarone; Prob, probenecid; DMSO, dimethylsulfoxide.