Functional expression of the renal organic cation transporter and P-glycoprotein inXenopus laevis oocytes

The hypothesis that P-glycoprotein (P-gp) mediates the renal secretion of organic cations was tested by functional expression of mRNAs in theXenopus laevis oocyte system. Efflux of 2-deoxytubercidin (dTub), a substrate for the renal organic cation transporter (OCT) but not for P-gp, was enhanced by injection of renal mRNA but not by injection of mRNA from P-gp-overexpressing cells (MDCK cells transduced with the cDNA for humanMDR1). The functional capacity of the MDCK-MDR mRNA was established by its ability to reduce, the steady-state uptake of a classical P-gp substrate, vinblastine. Thus, these data indicate OCT and P-gp to be distinct entities. TheXenopus oocyte system provides a functional approach to further characterize the OCT.Work supported by NIH Grant RO1DK41606 from the Institute for Digestive Diseases and Kidney, and NIH Cancer Center Core Grant, CA 16672 from the National Cancer Institute