POLARIZED EXPRESSION OF DRUG TRANSPORTERS

Most drug transporters are expressed in tissues with barrier functions such as the
liver, kidney, intestine, placenta, and brain. Cells at the border of these barriers are
usually polarized. For example, enterocytes of intestine and proximal tubule cells of
kidney have an apical domain facing the lumen and a basolateral domain facing the
blood circulation; hepatocytes polarize into a canalicular membrane facing the bile
duct and a sinusoidal membrane facing the blood circulation; syncytiotrophoblasts of
placenta have an apical domain facing maternal blood and a basolateral domain facing
the fetus. Brain capillary endothelial cells, which function as the blood–brain barrier,
also polarize into apical and basolateral membranes. In most cases, the expression of
drug transporters is highly restricted to one side (i.e., apical or basolateral domain)
of polarized cells. Such polarized expression of the transporters is essential for the
concerted transport of drugs in the same direction. One of the best studied examples of
concerted transport is the kidney. Kidney proximal tubule cells play a critical role in the
body clearance of drugs. These drugs are first taken up from the blood into the proximal
tubule cells by transporters at the basolateral membrane. Once inside the cells, these
drugs are then transported out of the cells into the tubule lumen by transporters at
the apical membrane and subsequently eliminated in the urine. The alliance between
transporters at both the basolateral membrane and the apical membrane of the kidney
proximal tubule cells ensures clearance of the drugs from the body.