TABLE 2.
Regulatory mechanisms and protein factors involved in transcription of solute carrier (SLC) drug transporter genes
Only those regulatory mechanisms/protein factors reviewed in the text are presented. The uppercase letters represent human proteins, whereas the others are rodent proteins.
| Regulatory Mechanism/ Protein Factor | Transporter | Representative Agonist/Activator | Representative Antagonist/ Inhibitor |
|---|---|---|---|
| DNA methylation | OATP1B1, OATP1B3, OATP3A1, OATP4A1, OATP3A1, OATP4C1, OATP2A1, Oatp1b2, Oatp1a1, Oatp1a6, Oatp1c1, Oatp1a4, OAT1, OAT3, Oat1, Oat3, OCT1, OCT2, OCT3, OCTN2, PEPT1, MATE1 | 5-Aza-2'-deoxy cytidine (5azadC), decitabine, metformin | |
| Histone modification | OATP2A1, OATP2A1, OATP1B1, OATP1B3, Oatp1b2, Oatp1a1, Oatp1a6, Oatp1c1, Oatp1a4, OAT2, OCT2, PEPT1, MATE2 | Histone deacetylase inhibitor: trichostatin, vorinostat (SAHA) | |
| PXR | Oatp2, OATP1B1, OATP1B3, OATP2B1, OATP2A1, OATP-A, OATP1A2, Oat1, Oat3, OCT1 | PCN, rifampicin, phenobarbital, doxorubicin, spironolactone | Methotrexate |
| AhR | Oatp2b1, Oatp3a1, OATP4C1, OATP1B1, OATP2B1, Oatp1a1, Oatp2, OAT1, OAT2 | TCDD, polychlorinated biphenyl 126, beta-naphthoflavone, diesel exhaust particles (DEPs), indoxyl sulfate, 3-methylcholanthrene | |
| CAR | OATP1A2, OATP1B3, OATP2B1, OATP1B3, Oatp1a1, Oatp1a4, Oatp2, OAT2, Oat1, Oat3 | Diallyl sulfide, phenobarbital, 6-(4-chlorophenyl)-imidazo [2,1-b] thiazole-5-, carbaldehyde-O-(3,4- dichlorobenzyl)oxime (CITCO) |
Methotrexate |
| FXR | OATP1B1, OATP1B3, OAT2, PEPT1, Pept1, MATE1, MATE2-K | Vitamin A, bile acids, CDCA, GW4064, fexaramine, berberine | DY268, Z-guggulsterone, glycine-β-muricholic acid, LPS |
| LXR | OATP1B1, Oatp1b2, OAT1, OAT2 | Oxysterols, berberine, TO-901317, GW3965, 22(R)-hydroxy-cholesterol, 22(S)-hydroxy-cholesterol, 9-cis retinoic acid (CRA), 25-hydroxy-cholesterol (HC) | |
| HIF-1α | OATP1B3, OATP1B3, OATP2B1 | ||
| HNF | OATP1B1, OATP1B3, Oatp1b2, Oatp1, Oatp2, Oatp1a1, Oatp1a4, Oatp1a5, Oatp1b2, Oatp2b1, Oatp1a1, Oatp1a6, Oatp2b1, Oatp3a1, Oatp4c1, Oatp2a1, OAT1, OAT2, OAT3, Oat1, Oat3, OCT1, Mate1 | LPS, UDCA | |
| Nrf2 | Oatp1a1, Oatp2b1, Oatp1b2, Oatp1a6, OAT2, Oat2, PEPT1, MATE1, MATE2-K | Sulforaphane | Retinoic acid, oltipraz |
| RXR | OATP1B1, OATP2B1, OCT1, OCTN2 | atRA, CRA | |
| RAR | OATP1B1, OATP2B1, OCT1 | atRA, CRA | |
| VDR | OATP1A2 | 1,25-Dihydroxyvitamin D3 (D3) | |
| PPARα | Oatp1a1, Oatp1a4, Oatp1b2, Oatp2a1, Oatp2b1, OCT1, OCT2, Oct2, OCTN2, Octn2, OCTN3, PEPT1, PepT1, Mate1 | Perfluorooctanoic acid, perfluorodecanoic acid, clofibrate, ciprofibrate, diethylhexylphthalate, fenofibrate | WY-14,643 |
| PPARγ | OCTN2 | Thiazolidinediones (troglitazone and rosiglitazone), luteolin | Bisphenol A diglycidyl ether (BADGE), GW9662 |
| Androgen receptor (AR) | Oct2 | Testosterone | |
| Estrogen receptor (ER) | OAT1, OCTN2 | Estrogen |