Basolateral and canalicular transport of xenobiotics in the hepatocyte: A review.

摘要: The molecular and functional characterization of severalproteins involved in the uptake excretion xenobioticsand endogenous compounds hepatocyte has been achievedthrough intensive research conducted past few years.These studies have lead to identification specificmembrane transporters located basolateral andcanalicular membrane domains hepatocyte. organicanion-transporting polypeptide (OATP), present thebasolateral hepatocyte, is responsible for thetranslocation xenobiotics from sinusoidal space into thehepatocyte. Once inside cell, unconjugated neutral, anionicand cationic can be secreted bile by themultidrug-resistance P-glycoprotein 1 (MDR1). Conjugatedxenobiotics (e.g. glucuronides glutathione conjugates) aresecreted canalicular multispecific organicanion transporter (cMOAT). Other play keyphysiological roles, including bilesalts (sodium-taurocholate cotransporter, NTCP) thesecretion conjugated salts(bile salt export pump, BSEP) phospholipids (MDR2).Experimental approaches used investigate role haveincluded both vivo vitro models. Animalmodels lacking include the`hyperbilirubinemic' rats (Groningen-Yellow (GY), Eisaihyperbilirubinemic (EHB) TR- rats), which aredeficient cMOAT protein, `knock-out' mice, lackingeither MDR1 or MDR2 transporter. Although no animal modelsare currently available study basolateraltransporters, their function conveniently investigatedthrough heterologous expression Xenopus laevis oocytesand also with vesicles isolated fromhepatocytes. total number canaliculartransport proteins still unknown,but current knowledge indicates that there are at least fourpresent five canaliculardomain. review focuses on knowledgeabout most relevant theuptake foreign sinusoidalspace active secretion bile. first partof deals (sinusoidal) transportof organic anions, major (e.g.NTCP, OATP) described here, terms knownbiochemistry physiology. In second part review,the (apical) transport anions isdiscussed biochemistry physiological MDR1,MDR2, BSEP detail. concludingremarks point out areas need addressedin order answer important questions remainunanswered this field study.