Modulators of the multidrug-transporter, P-glycoprotein, exist in the human plasma

P-glycoprotein (P-gp) is thought to mediate the transport of anticancer drugs and to be responsible for the multidrug-resistant (MDR) phenotype. P-gp is also expressed in normal human tissues, such as the adrenal gland, kidney, liver, colon and capillary endothelium of the brain. However, the function and transporting substrates of P-gp in normal tissues are still not understood. This paper explains that some compounds in the human plasma can modulate the transporting activity of P-gp. A partially purified fraction from the human plasma enhanced the accumulation of anti-cancer agents in MDR cells. This fraction inhibited the efflux of vinblastine from MDR cells, and also inhibited the photoaffinity labeling of P-gp with azidopine as effectively as vinblastine, quinidine and cepharanthine. The compounds in this purified fraction may be physiological substrates of P-gp and can probably overcome MDR.