Journal
TOXICOLOGY
Volume 153, Issue 1-3, Pages 203-219Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/S0300-483X(00)00315-2
Keywords
bile duct ligation; bile salt export pump; multidrug resistance
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Transport across hepatocyte plasma membranes is a key parameter in hepatic clearance and usually occurs through different carrier-mediated systems. Sinusoidal uptake of compounds is thus mediated by distinct transporters, such as Na+-dependent or Na+-independent anionic transporters and by some cationic transporters. Similarly, several membrane proteins located at the apical 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 excreted 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 hormones and xenobiotics. Moreover, a direct correlation between a defect and the absence of transporter with hepatic disease has been demonstrated for BSEP, MDR3-P-gp and MRP2. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
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