TY - JOUR T1 - Identification of the multidrug resistance-related P-glycoprotein as a cyclosporine binding protein. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 543 LP - 546 VL - 36 IS - 4 AU - B M Foxwell AU - A Mackie AU - V Ling AU - B Ryffel Y1 - 1989/10/01 UR - http://molpharm.aspetjournals.org/content/36/4/543.abstract N2 - The immunosuppressive agent cyclosporine A has been shown to reverse multidrug resistance (MDR) in malignant cells. In the present study, a 3H-cyclosporine diazirine analogue was used to photolabel viable MDR Chinese hamster ovary cells. The 170-kDa membrane P-glycoprotein, which functions as a drug efflux pump, was strongly labeled. The binding of 3H-cyclosporine diazirine analogue to P-glycoprotein was competable by excess cyclosporine A and by the nonimmunosuppressive cyclosporine H. These results suggest that cyclosporine reverses the MDR phenotype by binding directly to P-glycoprotein and that this binding is not dependent on the immunosuppressive potential of the cyclosporine derivative. The identification of P-glycoprotein as a cyclosporine binding protein has obvious implications for cancer chemotherapy. ER -