P-glycoprotein

P-glycoprotein (abbreviated as P-gp or Pgp) is a well characterized human ABC-transporter of the MDR/TAP subfamily. It is extensively distributed and expressed in normal cells such as those lining the intestine, liver cells, renal proximal tubular cells, and capillary endothelial cells comprising the blood-brain barrier. P-gp is also called ABCB1, ATP-binding cassette sub-family B member 1, MDR1, and PGY1.

Function
ABCB1 is an ATP-dependent efflux pump with broad substrate specificity. It likely evolved as a defence mechanism against harmful substances.

ABCB1 transports various substrates across the cell membrane including:
 * Drugs such as colchicine and tacrolimus
 * Chemotherapeutic agents such as etoposide, adriamycin, and vinblastine;
 * Lipids
 * Steroids
 * Xenobiotics
 * Peptides
 * Bilirubin
 * Cardiac glycosides like digoxin
 * Immunosuppressive agents
 * Glucocorticoids like dexamethasone
 * HIV-type 1 antiretroviral therapy agents like protease inhibitors and nonnucleoside reverse transcriptase inhibitors.

Its ability to transport the above substrates accounts for the many roles of ABCB1 including:
 * Regulating the distribution and bioavailability of drugs
 * Increased intestinal expression of P-glycoprotein can reduce the absorption of drugs that are substrates for P-glycoprotein. Thus, there is a reduced bioavailability, therapeutic plasma concentrations are not attained. On the other hand, supratherapeutic plasma concentrations and drug toxicity may result because of decreased P-glycoprotein expression
 * Active cellular transport of antineoplastics resulting in multidrug resistance to these drugs
 * The removal of toxic metabolites and xenobiotics from cells into urine, bile and the intestinal lumen
 * The transport of compounds out of the brain across the blood-brain barrier
 * Digoxin uptake
 * Prevention of ivermectin entry into the central nervous system
 * The migration of dendritic cells
 * Protection of hematopoietic stem cells from toxins.

Structure
Pgp is a 170 kDa transmembrane glycoprotein which includes 10-15 kDa of N-terminal glycosylation. The N-term half of the molecule contains 6 transmembrane domains, followed by a large cytoplasmic domain with an ATP binding site, and then a second section with 6 transmembrane domains and an ATP binding site which shows over 65% of amino acid similarity with the first half of the polypeptide.

History
ABCB1 was first cloned and characterized using its ability to confer a multidrug resistance phenotype to cancer cells that had developed resistance to chemotherapy drugs.