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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. More formally, it is an ATP-dependent efflux pump with broad substrate specificity. It exists in animals, fungi and bacteria and likely evolved as a defense mechanism against harmful substances. P-gp is extensively distributed and expressed in the intestinal epithelium where it pumps xenobiotics (such as toxins or drugs) back into the intestinal lumen, in liver cells where it pumps them into bile ducts, in the cells of the proximal tubule of the kidney where it pumps them into urine-conducting ducts, and in the capillary endothelial cells composing the blood–brain barrier and blood-testis barrier, where it pumps them back into the capillaries. Some cancer cells also express large amounts of P-gp, which renders these cancers multi-drug resistant. P-gp is a glycoprotein that in humans is encoded by the ''ABCB1'' gene. 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. P-gp was discovered in 1971 by Victor Ling. == Function == The protein belongs to the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). 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. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood–brain barrier.〔(【引用サイトリンク】 url =http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5243 )〕 P-gp transports various substrates across the cell membrane including: *Drugs such as colchicine, tacrolimus and quinidine *Chemotherapeutic agents such as etoposide, doxorubicin, 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 P-gp 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, and 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 and loperamide entry into the central nervous system *The migration of dendritic cells *Protection of hematopoietic stem cells from toxins.〔 It is inhibited by many drugs, such as: *Amiodarone *Azithromycin *Captopril *Clarithromycin *Cyclosporine *Piperine *Quercetin *Quinidine *Quinine *Reserpine *Ritonavir *Tariquidar *Verapamil 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「P-glycoprotein」の詳細全文を読む スポンサード リンク
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