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.[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.[5] 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.[6] Any such substance can sometimes be called a P-gp inhibitor.
P-gp was discovered in 1971 by Victor Ling.
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040584 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Ueda K, Clark DP, Chen CJ, Roninson IB, Gottesman MM, Pastan I (January 1987). "The human multidrug resistance (mdr1) gene. cDNA cloning and transcription initiation". The Journal of Biological Chemistry. 262 (2): 505–8. doi:10.1016/S0021-9258(19)75806-2. PMID 3027054.
- ^ Dean, Michael (2002-11-01). "The Human ATP-Binding Cassette (ABC) Transporter Superfamily". National Library of Medicine (US), NCBI. Archived from the original on 2006-02-12. Retrieved 2008-03-02.
- ^ Yu J, Zhou Z, Tay-Sontheimer J, Levy RH, Ragueneau-Majlessi I (September 2017). "Intestinal Drug Interactions Mediated by OATPs: A Systematic Review of Preclinical and Clinical Findings". Journal of Pharmaceutical Sciences. 106 (9): 2312–2325. doi:10.1016/j.xphs.2017.04.004. PMID 28414144.