Table 2.
Enterohepatic localization, transporter function, gene and corresponding protein name, and NRs that regulate the drug and bile-acid efflux transporters discussed in this review.
Gene | Protein | Function | Endogenous substrates | Exogenous substrates | Enterohepatic location | NR regulators |
---|---|---|---|---|---|---|
ABCB1 | MDR1/P-gp | ATP-dependent efflux | Vinblastine, paclitaxel, doxorubicin, etoposide, verapamil, digoxin, cyclosporine A (Klaassen and Lu, 2008), antiepileptics (Zhang et al., 2012), rifampicin, dexamethasone, and ritonavir (Cascorbi, 2011). For complete list, see Cheng and Klaassen (2006) | Apical membrane of enterocytes and hepatocytes (Klaassen and Lu, 2008; Cascorbi, 2011) | PXR VDR CAR |
|
OSTα/OSTβ | OSTα/OSTβ | Efflux | Bile acids (Dawson et al., 2005). estrone 3-sulfate, and prostaglandins (Klaassen and Aleksunes, 2010) | Digoxin (Klaassen and Aleksunes, 2010) | Basolateral membrane of hepatocytes and enterocytes (Klaassen and Lu, 2008) | FXR VDR |
ABCC2 | MRP2 | Efflux | Bilirubin, leukotriene C4, estrone 3-sulfate, and cholecystokinin (Keppler, 2011) | Ochratoxin A (Keppler, 2011), anthracyclines, Vinca alkaloids, methotrexate, and HIV protease inhibitors (Meijerman et al., 2008) | Apical membrane of hepatocyte and enterocyte (Klaassen and Lu, 2008) | PXR FXR CAR |
ABCC3 | MRP3 | Efflux | leukotriene C4, bilirubin, dehydroepiandrosterone 3-sulfate, and cholylglycine (Keppler, 2011) bile acids | Methotrexate, etopiside, taniposide, and epipodophyllotoxins (Meijerman et al., 2008) | Basolateral membrane of enterocytes and hepatocytes (Klaassen and Lu, 2008) | PXR FXR CAR |
ABCC4 | MRP4 | Efflux | Leukotrienes, Prostaglandins, Thromboxane B2, dehydroepiandrosterone 3-sulfate, and conjugated bile salts (Keppler, 2011) | Nucleotide analogs and methotrexate (Meijerman et al., 2008) | Basolateral membrane of hepatocytes (Klaassen and Lu, 2008) | CAR |
ABCG2 | BCRP | Efflux | dehydroepiandrosterone sulfate, estradiol-17β-glucuronide, and estrone 3-sulfate (Klaassen and Aleksunes, 2010) | Fluoroquinolones, statins, anticancer agents, and furosemide. For complete list, see Denson et al. (2001) | Apical membrane of hepatocytes and enterocytes (Klaassen and Lu, 2008) | PXR CAR |
ABCB11 | BSEP | Efflux | Conjugated and unconjugated bile acids | Apical membrane of hepatocytes (Klaassen and Lu, 2008) | FXR |
Also included are some (not all) substrates of each transporter.