What does P-glycoprotein transport?
P-glycoprotein is one of the drug transporters that determine the uptake and efflux of a range of drugs. P-glycoprotein functions as a transmembrane efflux pump, pumping its substrates from inside to outside the cell. Drugs which induce or inhibit P-glycoprotein can interact with other drugs handled by the pump.
What is the clinical relevance of P-glycoprotein P-gp?
The drug efflux transporter P-glycoprotein (P-gp) is known to confer multidrug resistance in cancer chemotherapy. Because of its expression and localization, it has been suggested that P-gp plays an important role in cancer chemotherapy, intestinal absorption, and brain uptake.
What is the impact of P-glycoprotein P-gp at the blood brain barrier?
Purpose: P-glycoprotein (Pgp) is an efflux transporter involved in transport of several compounds across the blood-brain barrier (BBB). Loss of Pgp function with increasing age may be involved in the development of age-related disorders, but this may differ between males and females.
What does P stand for in P-glycoprotein?
permeability glycoprotein
P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein of the cell membrane that pumps many foreign substances out of cells.
Is P-glycoprotein an active transporter?
P-glycoprotein (P-gp) is an ATP-binding cassette (ABC) transporter responsible for the multidrug resistance (MDR) phenotype when overproduced in the plasma membrane of tumor cells (1). P-gp exhibits an ATP hydrolysis activity, coupled to the efflux of a variety of hydrophobic molecules (2, 3).
What is a P-glycoprotein inhibitor?
P-gp is overexpressed on the surface of cancer cells and prevents drug accumulation inside the tumor, acting as the efflux pump. It extrudes anticancer drugs before they can reach the intended target. Further, it often mediates the development of resistance of the cells to anticancer drugs.
Does azithromycin inhibit P-glycoprotein?
Macrolides: Erythromycin, Azithromycin, and Clarithromycin The FDA approved macrolide antibiotics (erythromycin, azithromycin, and clarithromycin) were all reported as p-gp inhibitors. This has been supported by many studies in the literature (64–66).
What anticancer drugs would be affected by P-glycoprotein?
A plethora of anticancer drugs that are central to many chemotherapeutic regimes are susceptible to P-gp-mediated efflux (Figure 1), such as the microtubule-targeting vinca alkaloids (e.g. vinblastine and vincristine) and taxanes (paclitaxel and docetaxel), the DNA-chelating anthracyclines (doxorubicin and daunorubicin …
What is the blood brain barrier?
The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from non-selectively crossing into the extracellular fluid of the central nervous system where neurons reside.
Where is PGP present?
Pgp is located throughout the human body in organs or tissues with an excretory and/or barrier function, such as liver, kidney, testes and the BBB [4]. At the BBB, Pgp is highly expressed at the vessel walls of the brain capillaries, where it functions as an efflux pump.
Is glycoprotein on plasma membrane?
Glycoproteins are proteins that have sugar molecules attached to them. These sugar molecules are actually gathered into short chains, or oligosaccharides. The cell uses glycoproteins embedded in the plasma membrane to get the oligosaccharides on the outside of the cell.
What is P-glycoprotein role in multi drug resistant cancers?
P-glycoprotein (P-gp) is a well-identified membrane transporter with capability to efflux drug molecules out of the cancer cell leading to reduced efficiency of chemotherapy. Cancer cells upregulate P-gp expression as an adaptive response to evade chemotherapy mediated cell death.