Ntcp

Ntcp (Na⁺/Taurocholate cotransporting polypeptide; gene name Slc10a1) is the founding member of the SLC10 family of solute carrier proteins. Ntcp functions primarily as a hepatic Na⁺-bile acid symporter. The substrate specificity of Ntcp is fairly narrow and appears to be restricted to unconjugated bile acids, glycine- and taurine-conjugated bile acids, and steroid sulfate conjugates and iodothyronines. It is also specific for some drugs and drug conjugates, such as bromosulfophthalein, chlorambucil-taurocholate, and the HMG CoA reductase inhibitor rosuvastatin. Ntcp's expression at the basolateral (sinusoidal) membrane of hepatocytes and its high affinity for conjugated bile acids promotes their efficient extraction from portal blood. Thus, Ntcp functions to maintain the enterohepatic circulation of bile acids and keeps plasma concentration at a minimum. While Ntcp’s major physiological function is the hepatocytic transport of bile acids, Ntcp is also expressed at low levels on the luminal (apical) membrane of pancreatic acinar cells where it may function to clear any bile acids that leak into the terminal acini. Overwhelming evidence indicates that Ntcp accounts for most, if not all, hepatic Na⁺-dependent bile acid transport. Ntcp polymorphisms that are specific to different ethnic groups and interfere with bile acid transport in vitro have been reported for the human NTCP gene. Unfortunately, clinical data are not available for these subjects, leaving open the possibility that an isolated NTCP gene defect may be asymptomatic as the liver also expresses Na⁺-independent bile acid transporters as well as another potential Na⁺-dependent transporter.