Table 4.
Nomenclature, Location, and Function of the Major Hepatocyte and Cholangiocyte Membrane Transporters Involved in Bile Secretion
| Name | Abbreviation (gene) | Phase | Location | Function |
|---|---|---|---|---|
| Sodium-taurocholate cotransporter | NTCP (SLC10A1) | 0 | Basolateral membrane of hepatocytes | Primary carrier for conjugated bile-salt uptake from portal blood |
| Organic-anion-transporting polypeptides | OATPs (SLCO1B1and 1B3) | 0 | Basolateral membrane of hepatocytes | Broad substrate carriers for sodium-independent uptake of bile salts, organic anions, and other amphipathic organic solutes from portal blood |
| Organic solute transporter alpha/beta | OSTα/β | III | Basolateral membrane of hepatocytes, cholangiocytes, ileum, and proximal tubule of kidney | Heteromeric solute carrier for facilitated transport of bile salts across basolateral membrane of ileum. Expression induced in liver in cholestasis |
| Organic cation transporter-1 | OCT-1 (SLC22A1) | 0 | Basolateral Membrane of hepatocytes | Facilitates sodium-independent hepatic uptake of small organic cations |
| Organic anion transporter-2 | OAT-2 (SLC22A7) | 0 | Basolateral membrane of hepatocytes | Facilitates sodium-independent hepatic uptake of drugs and prostaglandins |
| Multidrug-resistance-1 P-glycoprotein* | MDR1 (ABCB1) | III | Canalicular and cholangiocyte apical membrane | ATP-dependent excretion of various organic cations, xenobiotics, and cytotoxins into bile; barrier function in cholangiocytes |
| Multidrug-resistance-3 P-glycoprotein (phospholipid transporter)* | MDR3 (ABCB4) | III | Canalicular membrane | ATP-dependent translocation of PC from inner to outer leaflet of membrane bilayer |
| Bile salt export pump* | BSEP (ABCB11) | III | Canalicular membrane | ATP-dependent bile-salt transport into bile; stimulates BSDF |
| Multidrug-resistance-associated protein 2 (canalicular multispecific organic-anion transporter)* | MRP2 (ABCC2) | III | Canalicular membrane | Mediates ATP-dependent multispecific organic-anion transport (e.g., bilirubin diglucuronide) into bile; contributes to bile salt-independent bile flow by GSH transport |
| Multidrug-resistance-associated protein 3* | MRP3 (ABCC3) | III | Basolateral membrane of hepatocytes and cholangiocytes | Expression induced in cholestasis. Transports bilirubin and bile acid glucuronide conjugates |
| Mulitdrug-resistance-associated protein 4* | MRP4 (ABCC4) | III | Basolateral membrane of hepatocyte; apical membrane of proximal tubule of kidney | Expression induced in cholestasis transports sulfated bile acid conjugates and cyclic nucleotides |
| Mulitdrug-resistance-associated protein-6* | MRP6 (ABCC6) | III | Basolateral membrane of hepatocyte | ATP-dependent transport of organic anions and small peptides. Mutations of MRP6 gene result in pseudoxanthoma elasticum |
| Breast cancer resistance protein* | BCRP (ABCG2) | III | Canalicular membrane, proximal tubule of kidney | ATP-dependent multispecific drug transporter, particularly sulfate cong; protoporphyrins are endogenous substrate. Substrate overlap with MRP2 |
| Sterolin-1 and 2* | ABCG5/G8 | III | Canalicular membrane and apical membrane of intestine | Heteromeric ATP-dependent transporter for cholesterol and plant sterols (e.g. sitosterol) |
| Multidrug and toxin extrusion protein 1 | MATE-1 (SLC47A1) | III | Canalicular membrane and brush border of kidney | Organic cation/H+ exchanger extrudes cationic xenobiotics |
*
These transporters are members of the ABC superfamily. Table reproduced, with permission, from Ref. (79).