Читать книгу Drug Transporters - Группа авторов - Страница 18

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 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 most well‐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 the clearance of the drugs from the body.