ABCB1 Pharmacogenetics: Progress, Pitfalls, and Promise
2007; Wiley; Volume: 81; Issue: 2 Linguagem: Inglês
10.1038/sj.clpt.6100052
ISSN1532-6535
AutoresLeslie W. Chinn, Deanna L. Kroetz,
Tópico(s)HIV/AIDS drug development and treatment
ResumoIn 1976, Juliano and Ling1 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
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