Table of Contents
What does P-glycoprotein do?
P-glycoprotein is one of the drug transporters that determine the uptake and efflux of a range of drugs. This process affects their plasma and tissue concentrations and ultimately their final effects. P-glycoprotein functions as a transmembrane efflux pump, pumping its substrates from inside to outside the cell.
Where is P-gp expressed?
P-gp is primarily expressed in the liver, kidney, gastrointestinal tract, and blood brain barrier. P-gp is located on the canalicular apical membrane of hepatocytes in the liver; on the brush border of proximal tubule cells in the kidney; and on the apical membrane of mucosal cells in the small intestine (3).
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.
What is the role of P-glycoprotein on pharmacokinetic aspects?
P-glycoprotein, the most extensively studied ATP-binding cassette (ABC) transporter, functions as a biological barrier by extruding toxins and xenobiotics out of cells. In vitro and in vivo studies have demonstrated that P-glycoprotein plays a significant role in drug absorption and disposition.
How do P-gp inhibitors work?
In general, P-gp can be inhibited by three mechanisms: (i) blocking drug binding site either competitively, non-competitively (Fig. 2) or allosterically; (ii) interfering with ATP hydrolysis; and (iii) altering integrity of cell membrane lipids.
What is its role in multi drug resistant cancers?
Multi-drug resistance (MDR) in the cancer chemotherapy has been pointed out as the ability of cancer cells to survive against a wide range of anti-cancer drugs 22. MDR mechanism may be developed by increased release of the drug outside the cells. So the drug absorption is reduced in these cells.
What is P-glycoprotein role in multi drug resistant cancers?
P-glycoprotein (P-gp) is a key player in the multidrug-resistant phenotype in cancer. The protein confers resistance by mediating the ATP-dependent efflux of an astonishing array of anticancer drugs.
Why are some cancers resistant to chemotherapy?
Resistance can occur when cancer cells—even a small group of cells within a tumor—contain molecular changes that make them insensitive to a particular drug before treatment even begins. Because cancer cells within the same tumor often have a variety of molecular changes, this so-called intrinsic resistance is common.
Why do some tumors not respond to chemo?
What is the function of P glycoprotein?
P-glycoprotein is one of the main energy-dependent efflux mechanisms in the cell membranes controlling drug absorption, distribution, and elimination in the body. Capillary endothelium cells in microvessels at the BBB contain high amounts of P-glycoprotein (Cordon-Cardo et al., 1989 ).
Does intestinal expression of P-glycoprotein affect drug absorption and bioavailability?
Increased intestinal expression of P-glycoprotein can reduce the absorption of drugs that are substrates for P-glycoprotein. Thus, there is a reduced bioavailability, and therapeutic plasma concentrations are not attained.
What is the function of PGP protein?
This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. P-gp is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity.