Figure 3.
Identification of potential endogenous Oat3 substrates. (A) Box plots of intensity values for two of the identified compounds from the metabolomic analysis, FMN and thymidine, and of an unknown compound of m/z of 323.03. **P < 0.01. (B) Tracer uptake into Oat3-expressing oocytes was determined in the presence of the indicated concentrations of the putative substrates, thymidine and FMN, and of the well-characterized Oat3 substrate estrone-3-sulfate and in their absence (control). Data are means ± SEM of measurements in four groups of four to five oocytes each, and the IC50 values were calculated by curve-fitting the points using nonlinear regression. (C) Uptake of labeled thymidine (0.097 μM) and ES (0.017 μM) was determined in oocytes microinjected with Oat3 and in control (noninjected) oocytes. Data are means ± SEM of measurements in five groups of four to eight oocytes each. Oat3-expressing oocytes manifested significantly greater uptake of both ES and thymidine than did control oocytes. #P < 0.001. (D) Intravenous application of thymidine induced a dosage-dependent reduction in BP in anesthetized WT and Oat3−/− mice. Data are means ± SEM in four mice. *P < 0.05, **P < 0.01, #P < 0.001 versus vehicle.