NA+-DEPENDENT AND NA+-INDEPENDENT BILE-ACID UPTAKE SYSTEMS IN THE LIVER

Expression cloning in Xenopus laevis oocytes was used to clone the Na+/taurocholate cotransporting polypeptide (Ntcp) and a Na+-independent organic anion transporting polypeptide (oatp) from rat liver. Ntcp is a glycoprotein of 362 amino acids, with a calculated molecular mass of 39 kD. It is predicted to span the membrane 7 times and is only expressed in differentiated hepatocytes of mammalian liver. Functionally, it mediates selective Na+-dependent bile acid uptake. oatp is a glycoprotein of 670 amino acids with a calculated molecular mass of 74 kD which is predicted to have 10 transmembrane domains. Functionally, oatp can mediate chloride-dependent and -independent bromosulfophthalein (BSP) uptake as well as Na+-independent bile acid transport. Neither Ntcp nor oatp demonstrate any significant homologies between each other and in comparison to other so far cloned transport proteins.