[4] P-gp is a well-characterized ABC-transporter (which transports a wide variety of substrates across extra- and intracellular membranes) of the MDR/TAP subfamily.

[9] The structure was derived from the mouse MDR3 gene product heterologously expressed in Pichia pastoris yeast.

The promiscuous binding pocket of P-gp is lined with aromatic amino acid side chains.

Through Molecular Dynamic (MD) simulations, this sequence was proved to have a direct impact in the transporter's structural stability (in the nucleotide-binding domains) and defining a lower boundary for the internal drug-binding pocket.

[11] P-gp is expressed primarily in certain cell types in the liver, pancreas, kidney, colon, and jejunum.

P-gp is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity.

[14] P-gp transports various substrates across the cell membrane including: Its ability to transport the above substrates accounts for the many roles of P-gp including: It is inhibited by many drugs, such as amiodarone, azithromycin, captopril, clarithromycin, cyclosporine, piperine, quercetin, quinidine, quinine, reserpine, ritonavir, tariquidar, and verapamil.

[31] Some common pharmacological inhibitors of P-glycoprotein include: amiodarone, clarithromycin, ciclosporin, colchicine, diltiazem, erythromycin, felodipine, ketoconazole,[32] lansoprazole, omeprazole and other proton-pump inhibitors, nifedipine, paroxetine, reserpine,[33] saquinavir,[32] sertraline, quinidine, tamoxifen, verapamil,[34] and duloxetine.

[36] Common pharmacological inducers of P-glycoprotein include carbamazepine, dexamethasone, doxorubicin, nefazodone, phenobarbital, phenytoin, prazosin, rifampicin, St. John's wort, tenofovir, tipranavir, trazodone, and vinblastine.

Some of these substrates include colchicine, ciclosporin, dabigatran,[33] digoxin, diltiazem,[38] fexofenadine, indinavir, morphine, and sirolimus.

[39] Altered P-gp function has also been linked to inflammatory bowel diseases (IBD);[40] however, due to its ambivalent effects in intestinal inflammation many questions remain so far unanswered.

[41] Mice deficient in MDR1A develop chronic intestinal inflammation spontaneously, which appears to resemble human ulcerative colitis.

[42] P-gp efflux activity is capable of lowering intracellular concentrations of otherwise beneficial compounds, such as chemotherapeutics and other medications, to sub-therapeutic levels.

Consequently, P-gp overexpression is one of the main mechanisms behind decreased intracellular drug accumulation and development of multidrug resistance in human multidrug-resistant (MDR) cancers.

A Homozygous genotype for the allele ABCB1/MDR1 is capable of a higher absorption from the blood vessels and a lower extrusion into the lumen.

[50] This article incorporates text from the United States National Library of Medicine, which is in the public domain.