Comparative net transport ratios for a variety of human and rat renal transporters mediating in vitro transport of tanshinol
The concentrations of methotrexate for BCRP and Bcrp were 100 μM. The concentration of probenecid to inhibit OAT2- and Oat2-mediated transport of prostaglandin F2α was 10 mM. Net transport ratios represent the mean ± S.D. (n = 3). When the net transport ratio was >3 (for the solute carrier family transporters) or >2 (for the ABC transporters), there were statistically significant differences between TransportTC and TransportMC or between TransportATP and TransportAMP (P < 0.05).
| Transporter | Positive Substrate (10 μM) | Tanshinol (100 μM) | ||||
|---|---|---|---|---|---|---|
| Substrate | Not Treated with Any Inhibitor | Treated with 1 mM Positive Inhibitor | Treated with 1 mM Tanshinol as Inhibitor | Not Treated with Any Inhibitor | Treated with 1 mM Positive Inhibitor | |
| Human renal SLC transporters | ||||||
| OAT1 | Para-aminohippuric acid | 146.9 ± 22.0 | 1.7 ± 0.1 (Probenecid) | 15.1 ± 2.7 | 164.0 ± 4.3 | 4.6 ± 0.4 (Probenecid) |
| OAT2 | Prostaglandin F2α | 68.0 ± 4.6 | 7.6 ± 0.8 (Probenecid) | 23.9 ± 1.6 | 80.7 ± 3.1 | 6.7 ± 0.7 (Probenecid) |
| OAT3 | Estrone-3-sulfate | 23.9 ± 1.8 | 1.9 ± 0.3 (Probenecid) | 10.3 ± 2.8 | 4.6 ± 0.4 | 1.2 ± 0.1 (Probenecid) |
| OAT4 | Estrone-3-sulfate | 14.1 ± 1.0 | 3.0 ± 0.6 (Probenecid) | 8.3 ± 1.5 | 7.3 ± 1.5 | 0.9 ± 0.3 (Probenecid) |
| OATP4C1 | Estrone-3-sulfate | 5.7 ± 0.7 | 2.3 ± 0.4 (Probenecid) | 5.4 ± 0.2 | 1.2 ± 0.2 | ― |
| OCT2 | Tetraethylammonium | 103.2 ± 10.7 | 46.1 ± 4.7 (Cimetidine) | 105.7 ± 8.9 | 1.4 ± 0.2 | ― |
| OCTN1 | Tetraethylammonium | 7.9 ± 0.2 | 0.5 ± 0.1 (Verapamil) | 7.4 ± 0.2 | 1.5 ± 0.2 | ― |
| MATE1 | Tetraethylammonium | 60.9 ± 2.0 | 0.5 ± 0.1 (Cimetidine) | 63.2 ± 1.0 | 0.8 ± 0.2 | ― |
| MATE2-K | Tetraethylammonium | 3.9 ± 0.4 | 0.6 ± 0.1 (Cimetidine) | 5.3 ± 0.6 | 1.9 ± 0.6 | ― |
| Human renal ABC transporters | ||||||
| MRP2 | Estradiol-17β-D-glucuronide | 24.2 ± 0.5 | 3.7 ± 0.1 (indomethacin) | 17.1 ± 0.5 | 2.3 ± 0.4 | ― |
| MRP4 | Estradiol-17β-D-glucuronide | 20.2 ± 0.7 | 4.4 ± 0.8 (indomethacin) | 15.9 ± 0.3 | 1.7 ± 0.2 | ― |
| BCRP | Methotrexate | 17.7 ± 0.1 | 4.1 ± 0.3 (novobiocin) | 17.9 ± 0.3 | 1.0 ± 0.3 | ― |
| Rat renal SLC transporters | ||||||
| Oat1 | Para-aminohippuric acid | 58.8 ± 4.1 | 1.7 ± 0.1 (Probenecid) | 7.8 ± 0.9 | 198.2 ± 22.0 | 3.4 ± 0.1 (Probenecid) |
| Oat2 | Prostaglandin F2α | 22.1 ± 1.6 | 1.8 ± 0.4 (Probenecid) | 20.0 ± 0.7 | 17.9 ± 3.8 | 2.5 ± 0.7 (Probenecid) |
| Oat3 | Estrone-3-sulfate | 27.0 ± 7.3 | 1.3 ± 0.6 (Probenecid) | 9.7 ± 1.9 | 5.0 ± 0.3 | 0.9 ± 0.2 (Probenecid) |
| Oct1 | Tetraethylammonium | 102.1 ± 10.5 | 46.9 ± 3.2 (Cimetidine) | 99.1 ± 9.8 | 1.6 ± 0.7 | ― |
| Octn1 | Tetraethylammonium | 6.1 ± 0.1 | 0.7 ± 0.1 (Verapamil) | 6.4 ± 0.2 | 1.3 ± 0.3 | ― |
| Octn2 | Tetraethylammonium | 59.2 ± 3.0 | 1.3 ± 0.1 (Verapamil) | 61.6 ± 1.1 | 2.3 ± 0.6 | ― |
| Oct2 | Tetraethylammonium | 95.2 ± 10.1 | 41.2 ± 7.4 (Cimetidine) | 93.3 ± 8.3 | 1.3 ± 0.3 | ― |
| Mate1 | Tetraethylammonium | 22.1 ± 0.3 | 0.6 ± 0.1 (Cimetidine) | 19.3 ± 0.5 | 1.0 ± 0.2 | ― |
| Rat renal ABC transporters | ||||||
| Mrp2 | Estradiol-17β-D-glucuronide | 10.2 ± 3.2 | ― | ― | 1.8 ± 0.1 | ― |
| Mrp4 | Estradiol-17β-D-glucuronide | 11.4 ± 1.3 | ― | ― | 2.2 ± 0.2 | ― |
| Bcrp | Methotrexate | 43.4 ± 10.2 | ― | ― | 1.0 ± 0.2 | ― |