© 2001 Kluwer Academic Publishers. Printed in the Netherlands. 225 Basolateral and canalicular transport of xenobiotics in the hepatocyte:

The molecular and functional characterization of several proteins involved in the uptake and excretion of xen-obiotics and endogenous compounds in the hepatocyte has been achieved through intensive research conducted in the past few years. These studies have lead to the identification of specific membrane transporters located in the basolateral and canalicular membrane domains of the hepatocyte. The organic anion-transporting polypeptide (OATP), present in the basolateral membrane of the hepatocyte, is responsible for the translocation of xenobiotics from the sinusoidal space into the hepatocyte. Once inside the cell, unconjugated neutral, anionic and cationic xenobiotics can be secreted into bile by the multidrug-resistance P-glycoprotein 1 (MDR1). Conjugated xenobiotics (e.g. glucuronides and glutathione conjugates) are secreted into bile by the canalicular multispecific organic anion transporter (cMOAT). Other transporters play key physiological roles, including the basolateral uptake of bile salts (sodium-taurocholate cotransporter, NTCP) and the secretion into bile of conjugated and unconjugated bile salts (bile salt export pump, BSEP) and phospholipids (MDR2). Experimental approaches used to investigate the role of the basolateral and canalicular transporters in the hepatocyte have included both in vivo and in vitro models. Animal models lacking canalicular transporters include the ‘hyperbilirubinemic ’ rats (Groningen-Yellow (GY), Eisai hyperbilirubinemic (EHB) and TR − rats), which are deficient in the cMOAT protein, and ‘knock-out ’ mice