Физиологические и клинические аспекты Р-гликопротеина

Modern conceptions about P-glycoprotein (Pgp) which is a big transmembrane protein transporting a variety of cytotoxic substances are presented in the literature review. Pgp belongs to the protein family of ABC transporters and is a product of MDR1 gene. Pgp is located on the surface of epithelium of small and large intestine, pancreatic duct, in the bile canaliculuses of the liver, bronchi, in the renal and adrenal gland proximal ducts, as well as in the endothelial cells of histohematogenous barriers (blood-brain, blood-testicular and blood-ovarian barriers) and of placenta. The physiological role of Pgp is the protection of cells from different toxic substances and metabolites. It transports the variety of compounds. The level of Pgp activity may influence the efficiency of the therapy significantly because a lot of drugs (glucocorticosteroids, anti tumor drugs, macrolides, statins, etc.) are the substrates of Pgp. A number of drugs can inhibit or induct the Pgp activity. At simultaneous application of Pgp inhibitors and drugs the concentration of the latter may increase and so the risk of unfavorable reactions also grows. On the other hand, the therapy by standard drugs doses may be not effective enough at combination with P-glycoprotein inductors as some of the substrates can inhibit it. P-glycoprotein is one of the most important mechanisms of multidrug resistance development