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Concept
P-glycoprotein
Summary
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 it 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 urinary filtrate (in the proximal tubule), and in the capillary endothelial cells composing the blood–brain barrier and blood–testis barrier, where it pumps them back into the capillaries.
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. The normal excretion of xenobiotics back into the gut lumen by P-gp pharmacokinetically reduces the efficacy of some pharmaceutical drugs (which are said to be P-gp substrates). In addition, some cancer cells also express large amounts of P-gp, further amplifying that effect and rendering these cancers multidrug resistant. Many drugs inhibit P-gp, typically incidentally rather than as their main mechanism of action; some foods do as well. Any such substance can sometimes be called a P-gp inhibitor.
P-gp was discovered in 1971 by Victor Ling.
A 2015 review of polymorphisms in ABCB1 found that "the effect of ABCB1 variation on P-glycoprotein expression (messenger RNA and protein expression) and/or activity in various tissues (e.g. the liver, gut and heart) appears to be small.
Official source
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