IDENTIFICATION OF THE SYNTHETIC SURFACTANT NONYLPHENOL ETHOXYLATE - AP-GLYCOPROTEIN SUBSTRATE IN HUMAN URINE

P-glycoprotein (Mdr1p) is an ATP-dependent drug efflux pump that is ov erexpressed in multidrug-resistant cells and some cancers. Mdr1p is al so expressed in normal tissues like the kidney, where it can mediate t ransepithelial drug transport. A human urinary compound that reverses multidrug resistance and blocks [H-3]azidopine photolabeling of P-glyc oprotein was purified to homogeneity and identified by H-1-NMR and mas s spectrometry as the synthetic surfactant nonylphenol ethoxylate (NPE ). Multidrug-resistant Chinese hamster ovary (CHO) C5 cells accumulate d less [H-3]NPE than parental drug-sensitive Aux-B1 cells, and Mdr1p s ubstrates, verapamil and cyclosporin A, increased this surfactant's ac cumulation in C5 cells. NPE blocked the net transepithelial transport (basolateral to apical) of [H-3]cyclosporin A in epithelia formed by M adin-Darby canine kidney (MDCK) cells. Net transepithelial transport ( basal to apical) of [H-3]NPE was demonstrated in MDCK cells and was in hibited by cyclosporin A. These findings show NPE is a Mdr1p substrate excreted into urine by kidney P-glycoprotein. NPE is a widely used su rfactant and a known hormone disrupter that is readily absorbed orally or topically. The current findings indicate the function of kidney Md r1p may be to eliminate exogenous compounds from the body.