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ABCB1 Pharmacogenetics: Progress, Pitfalls, and Promise
Author(s) -
Chinn L W,
Kroetz D L
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100052
Subject(s) - p glycoprotein , chinese hamster ovary cell , atp binding cassette transporter , transporter , efflux , biology , xenobiotic , pharmacology , colchicine , drug metabolism , drug , gene , receptor , biochemistry , drug resistance , multiple drug resistance , genetics , enzyme
In 1976, Juliano and Ling 1 reported expression of a 170 kDa protein in colchicine‐resistant Chinese hamster ovary (CHO) cells that was absent in drug‐sensitive cells. Because this protein altered cellular permeability to colchicine, the authors named it P‐glycoprotein (P‐gp). 1 P‐gp overexpression was described in tumor samples and leukemic cells. 2 High homology with bacterial transporters suggested that P‐gp was an efflux transporter, modulating intracellular xenobiotic concentrations. 3 In 1986, the gene encoding P‐gp was discovered and designated MDR1 (HUGO name ABCB1 ). 4 Immunohistochemical studies demonstrated P‐gp expression in tissues with secretory or excretory functions (liver, kidney, and gastrointestinal tract) and at blood‐tissue barrier sites, such as the blood‐brain barrier. 5 This pattern of expression indicated that P‐gp may influence xenobiotic response and toxicity, either through pharmacokinetic or pharmacodynamic effects. 6 Clinical Pharmacology & Therapeutics (2007) 81 , 265–269. doi: 10.1038/sj.clpt.6100052