Dynamic localization of hepatocellular transporters in health and disease

Figure 1 Localization and function of sinusoidal and canalicular hepatocellular transporters. A: humans; B: rodents. The Na⁺-dependent sinusoidal uptake of bile salts is mediated by NTCP (human)/Ntcp (rat). The Na⁺-independent hepatic uptake of organic anions (OA^-), Bile salts and type II organic cations (OC⁺) is mediated by members of the OATP/Oatp family. Sinusoidal uptake of type I OC⁺ is mediated by OCT1/Oct1. Transport across the canalicular membrane is driven mainly by ATP-dependent export pumps (black circles). MDR1/Mdr1a, Mdr1b mediates canalicular excretion of amphiphilic type II OC⁺ and other hydrophobic compounds. MDR3/Mdr2 functions as a phosphatidylcholine (PC) flippase. BSEP/Bsep mediates apical excretion of BSs. MRP2/Mrp2 transports non-bile-salt organic anions, such as bilirubin glucuronides, GSH, and sulfated/glucuronidated bile salts. Canalicular transport of HCO₃^- is mediated by the Cl^-/HCO₃^- exchanger AE2/Ae2. Aquaporins AQP9 and AQP8 are involved in the transport of water across the rat sinusoidal and the canalicular membrane, respectively. The nature of the water channels in human liver has yet to be characterized.