Participation of the multispecific organic anion transporter in hepatobiliary excretion of glutathione S-conjugates, drugs and other xenobiotics

Abstract

Polarized liver cells, hepatocytes, are involved in carbohydrate, protein and fat metabolism, breakdown of hemoglobin and production of bile. They are also involved in overall detoxification processes in an organism associated with the transport of bile salts, cholesterol, phospholipids, endo- and xenobiotics, end-products of cellular metabolism and ions through the canalicular region of the hepatocyte plasma membrane. Uptake of the above-mentioned compounds into hepatocytes through the basolateral region of plasma membrane is followed by their chemical modification by enzymes of detoxification phase I (e.g. cytochromes P-450) and phase II (e.g. glutathione S-transferases). Canalicular transport participates in phase III of detoxification, and the molecular machinery involved in this process is localized in the canalicular region of the plasma membrane. Canalicular transport includes the following transport systems: a specific canalicular transporter for bile salts, a multidrug resistance 2 P-glycoprotein (MDR2) participating in the transport of lipids, a multidrug resistance 3 P-glycoprotein (MDR3) responsible for the transport of organic cations and the multispecific organic anion transporter (cMOAT) involved in the transport of non-bile acid organic anions. The cMOAT transport system is discussed in this detailed review.