TABLE 1.
Ki values for a set of chosen zebrafish Oatp1d1 interactors
Interaction of Oatp1d1 with typical endo- and xenobiotic substrates and inhibitors of OATP1/Oatp1 family is expressed as a percentage of LY uptake mediated by Oatp1d1-overexpressing HEK293 cells in the presence of an interactor (100 μm) relative to control (Oatp1d1-overexpressing HEK293 cells in the absence of an interactor). Physiological interactors are separated from xenobiotic interactors as shown. LY (5 μm) uptake was measured after a 15-min incubation at 37 °C. The inhibition constant (Ki) for each interactor that showed more than 50% inhibition was determined by fitting data to a sigmoidal four-parameter dose-response model (variable slope) in GraphPad Prism version 5. Mean, S.D., and confidence intervals are calculated from triplicate determinations. NE, no effect; ND, not determined.
| Compound | LY uptake |
Ki | c.i. | |
|---|---|---|---|---|
| Mean | S.D. | |||
| % | μm | |||
| Control | 100 | 0.10 | ||
| Estrone 3-sulfate | 1.04 | 0.20 | 1.01 | 0.75–1.37 |
| E17β-glucuronide | 2.25 | 0.10 | 3.26 | 2.83–3.75 |
| 17β-estradiol | 16.8 | 5.79 | 2.83 | 2.27–3.51 |
| 17a-ethinylestradiol | 0.20 | 0.14 | 5.93 | 4.41–7.97 |
| Progesterone | 0.67 | 0.88 | 9.06 | 8.06–10.2 |
| DHEAS | 0.21 | 0.15 | 0.68 | 0.46–0.99 |
| Androstenedione | 6.33 | 1.40 | 3.78 | 2.85–5.02 |
| Testosterone | 28.6 | 0.51 | 30.0 | 25.5–35.2 |
| Dihydrotestosterone | 18.0 | 0.23 | 23.4 | 18.6–29.3 |
| Cortisol | 65.0 | 0.04 | 120 | 73.8–194 |
| Corticosterone | 37.2 | 0.92 | 105 | 38.0–288 |
| Cholesterol | 109 | 2.48 | NE | NE |
| Pregnenolone | 68.2 | 1.89 | ND | ND |
| Thyroxine | 95.2 | 1.19 | NE | NE |
| Triiodotyronine | 31.4 | 4.41 | 42.7 | 18.9–95.9 |
| Prostaglandin E2 | 57.7 | 1.30 | 227 | 98.7–524 |
| Cholate | 34.7 | 2.39 | 141 | 33.8–591 |
| Deoxycholate | 0.18 | 0.07 | 9.94 | 6.53–15.1 |
| Taurocholate | 18.6 | 0.37 | 36.9 | 30.2–45.1 |
| Taurochenodeoxycholate | 0.28 | 0.09 | 3.40 | 2.66–4.33 |
| Bilirubin | 12.0 | 1.41 | 14.5 | 12.8–16.5 |
| Bromosulfophthalein | 0.11 | 0.01 | 2.99 | 2.19–4.06 |
| Ouabain | 109 | 1.16 | NE | NE |
| Methotrexate | 63.8 | 1.36 | 222 | 62.4–792 |
| Rifampicin | 0.19 | 0.04 | 12.7 | 9.86–16.2 |
| Pravastatin | 1.98 | 4.15 | 9.27 | 6.75–12.7 |
| Erythromycin | 76.5 | 3.06 | 882 | 640–1,216 |
| Benzylpenicillin | 42.8 | 3.41 | 372 | 271–510 |
| Probenecid | 23.0 | 0.67 | 26.0 | 14.5–46.6 |
| Cyclosporine A | 0.17 | 0.06 | 1.34 | 1.19–1.50 |
| Warfarin | 0.11 | 0.13 | 0.36 | 0.31–0.42 |
| Gemfibrozil | 10.2 | 0.20 | 7.44 | 4.37–12.7 |
| Bezafibrate | 66.7 | 1.16 | 40.4 | 22.9–71.4 |
| Fenofibrate | 25.9 | 1.48 | 54.4 | 37.8–78.3 |
| Clofibrate | 20.9 | 3.94 | 345 | 252–470 |