Fig. 5.

Effect of previously published OSTα/β inhibitors (A and C) and compounds that inhibit other bile acid transporters or compounds known to be associated with cholestatic liver injury (B and D) on OSTα/β-mediated TCA uptake. OSTab and Mock cells were preincubated with ECF Na− buffer (10 min at 37°C, pH 7.4), and uptake (30 s at 37°C) was initiated by addition of [³H]TCA (300 nCi/ml, 4 µM). Compounds were added only in the uptake phase (A and B) or only in the preincubation (10 min) phase (C and D). In A and C, concentration of known OSTα/β inhibitors was kept the same as previously published [200 μM: E₁S, indomethacin, spironolactone, sulfobromophthalein, taurolithocholic acid sulfate (TLCAS); 500 μM: DIG; 1,000 μM: probenecid]. B and D: the other compounds were tested at 100 μM. Background levels derived from Mock cells were subtracted, and uptake measurements were normalized to total cell protein. Values (means ± SD from 3 independent experiments) are expressed as percentage of vehicle control. GCDCA, glycochenodeoxycholic acid. ****P = 0.0001; ***P < 0.0005; **P < 0.005; *P < 0.05.