Table 1.
Bile acid transporters found in the brain.
| Bile acid transporter | Localization | References | Function and substrate forms |
|---|---|---|---|
| MRP2 | Apical/Basolateral Brain endothelial cells in mouse and rat | Miller et al., 2000; Soontornmalai et al., 20061 | The ABC family are active efflux pumps that transport chemicals through a membrane. Substrates include: TCA and its sulfated forms. |
| MRP3 | Tight junction of Choroid Plexus in mouse | Soontornmalai et al., 20061 | Substrates include: preferably conjugated bile acids. |
| MRP4 | Apical Brain Capillary endothelial cells in rat and human | Nies et al., 2004; Roberts et al., 20081 | Substrates include: CA and conjugated bile acids. |
| OSTα/OSTβ | No reports on mRNA or protein in brain, minimal mRNA found in mice | Klaassen and Aleksunes, 2010; Ballatori, 2011 | In the intestine, OSTα/β transports bile acids across the basolateral membrane of the enterocyte: releasing them to the portal vein. |
| BSEP | mRNA expression in rat choroid plexus is ~2.75% of hepatic Bsep expression | Choudhuri et al., 2003 | In the liver, BSEP is an active transport mechanism across the canalicular membrane of the hepatocyte: secreting conjugated bile acids into the bile ducts. |
| OATP1A1 | Apical Choroid plexus epithelial cells in rat | Angeletti et al., 19971 | The SLC family are typical uptake transporters even though some can function bidirectional. Substrates include: unconjugated and conjugated bile acids. |
| OATP1A4 | Basolateral Choroid plexus epithelial cells in rat; mRNA in brains of male and female C57BL/6 mice | Gao et al., 1999; Cheng et al., 20051 | Substrates include: unconjugated and conjugated bile acids. |
| OATP1A2 | In brain capillary endothelial cells in human, but not determined what side | Lee et al., 20051 | Substrates include: unconjugated and conjugated bile acids |
| OAT3 | Basolateral Brain Capillary endothelial cells in rat | Kikuchi et al., 2003; Roberts et al., 20081 | Substrates include: unconjugated and conjugated CA. |
| NTCP | mRNA expression in rat choroid plexus is ~1.8% of hepatic Ntcp expression | Choudhuri et al., 2003 | In the liver, NTCP transports bile acids across the basolateral membrane of the hepatocyte in a sodium-dependent manner: facilitating uptake of unconjugated and conjugated bile acids from the portal blood. |
| ASBT | Rat and mouse hypothalamus and frontal cortex, low mRNA expression in human brain and rat choroid plexus | Choudhuri et al., 2003; Klaassen and Aleksunes, 2010; McMillin et al., 2015; Nizamutdinov et al., 2017 | In the intestine, ASBT transports bile acids across the apical membrane of ileal enterocytes in a sodium-dependent manner: absorption of unconjugated and conjugated bile acids from the intestine. ASBT on the apical surface of cholangiocytes participate in the cholehepatic recirculation. ASBT in the brain could facilitate uptake of bile acids into neurons and other brain cells. Subsequently, intracellular bile acids could activate nuclear receptor. |
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References are according to Klaassen and Aleksunes (2010). ABC, ATP-binding cassette transporters; MRP, multidrug resistant protein; OST, organic solute transporter; BSEP, bile salt export pump; SLC, solute carriers; OATP, organic anion transporting polypeptide; OAT, organic anion transporter; NTCP, Na+ taurocholate cotransporting polypeptide; ASBT, apical sodium-dependent bile acid.