Hepatic canalicular membrane 4: expression of the multidrug resistance genes in the liver.

The liver is presented with a diverse set of nutrients, endogenous metabolites, and xenobiotics it must process for movement to their correct physiologic destinations. These compounds are transported by specific mechanisms that move their substrates, often against a concentration gradient. Several hepatic transporters have been identified such as the multispecific anion transporter, cMOAT, bile acid transporters, ion-motive ATPases, glutathione transporters, purine transporters, and the multidrug resistance-related protein, MRP. This review focuses on the hepatic regulation of the multidrug resistance genes that encode the P-glycoprotein transporters. P-glycoproteins are ATP-dependent integral membrane proteins that have diverse functions such as conferring resistance toward chemotherapeutic drugs and phospholipid movement. The expression of the multidrug resistance genes is regulated in a tissue-specific pattern and can be induced by exposure to chemotherapeutic drugs as well as cytotoxic xenobiotics. The specific molecular mechanisms that govern expression of these genes in normal and neoplastic cells are currently being unraveled.