ABCB1 pharmacogenetics: progress, pitfalls, and promise.
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)
Chinn
L W
LW
Department of Biopharmaceutical Sciences and Institute for Human Genetics, University of California San Francisco, San Francisco, California, USA.
Kroetz
D L
DL
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D035843:Biomedical Research / Q000379:methods / Q000639:trends; D020022:Genetic Predisposition to Disease; D006801:Humans; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism; D010597:Pharmacogenetics / Q000379:methods* / Q000639:trends; D011110:Polymorphism, Genetic
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027361:Organic Anion Transporters