Table 1.
IC50 values of various drugs tested on MRP4-mediated [14C]urate transport
| Drugs | MRP4-mediated urate transport (μM) |
|---|---|
| Furosemide | 1.29±0.01 |
| Bumetanide | NI |
| Torasemide | NI |
| Chlorothiazide | 0.24 × 10−3±0.005 × 10−3 (H) |
| 10.4±0.1 (L) | |
| Hydrochlorothiazide | 1.9±0.1 (H) |
| 220±3 (L) | |
| Salicylate | 2.1±0.1 (H) |
| 1547±25 (L) | |
| Sulfinpyrazone | 0.16±0.02 (H) |
| 40±1 (L) | |
| Benzbromarone | 0.104±0.01 (H) |
| 15.6±0.2 (L) | |
| Probenecid | 132±0.2a |
| Allopurinolb | NI |
| Oxypurinolb | NI |
Abbreviation: NI, no inhibition.
Membrane vesicles were incubated with 100 μM [14C]urate at 37 °C for 10 min, in the presence or absence of different concentrations of the drugs tested. [14C]urate uptake was measured by subtracting the background (AMP) from the ATP-dependent uptake. Each value represents the mean±s.e.mean of data obtained from three separate experiments, each performed in triplicate, calculated by non-linear regression analysis of the data from Figures 5 and 6. High (H)- and low (L)-affinity IC50 were determined according to a two-site competition model.
At low probenecid concentration (0.1 μM), urate transport was stimulated by 132±8%.
Stimulation of urate transport by190±50% at 200 μM allopurinol, and 136±17% at 100 μM oxypurinol, respectively.