Expression and regulation of hepatic drug and bile acid transporters

Transport across hepatocyte plasma membranes is a key parameter in hepatic clearance and usually occurs through different carrier-mediated systems. Si nusoidal uptake of compounds is thus mediated by distinct transporters, suc h as Na+-dependent or Na+-independent anionic transporters and by some cati onic transporters. Similarly, several membrane proteins located at the apic al pore of hepatocytes have been incriminated in the excretion of compounds into the bile. Indeed, biliary elimination of anionic compounds, including glutathione S-conjugates, is mediated by MRP2, whereas bile salts are excr eted by a bile salt export pump (BSEP) and Class I-P-glycoprotein (P-gp) is involved in the secretion of amphiphilic cationic drugs, whereas crass II- P-gp is a phospholipid transporter. The expression of hepatic transporters and their activity are regulated in various situations, such as ontogenesis , carcinogenesis, cholestasis, cellular stress and after treatment by hormo nes and xenobiotics. Moreover, a direct correlation between a defect and th e absence of transporter with hepatic disease has been demonstrated for BSE P, MDR3-P-gp and MRP2. (C) 2000 Elsevier Science Ireland Ltd. All rights re served.