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  • Title: Nucleoside transport in brush border membrane vesicles from human kidney.
    Author: Gutierrez MM, Brett CM, Ott RJ, Hui AC, Giacomini KM.
    Journal: Biochim Biophys Acta; 1992 Mar 23; 1105(1):1-9. PubMed ID: 1567888.
    Abstract:
    The goal of this study was to elucidate the mechanisms of nucleoside transport in the brush border membrane of the human kidney. [3H]Uridine was transported into brush border membrane vesicles (BBMV) from human kidney via Na(+)-independent and Na(+)-dependent processes. The Na(+)-dependent transport was saturable (Km = 4.76 +/- 0.39 microM; Vmax = 6.42 +/- 0.17 pmol/mg proteins per s) and was trans-stimulated by unlabeled uridine. Structural analogs of uridine (100 microM), 2'-deoxyuridine (2-dU) and dideoxyuridine (ddU), significantly inhibited Na(+)-uridine uptake into BBMV. Previous studies have suggested that Na(+)-nucleoside co-transport occurs via two major systems (Vijayalakshmi et al. (1988) J. Biol. Chem. 263, 19419-19423). One system (cit) is generally pyrimidine-selective; thymidine serves as a model substrate. The other system (cif) is generally purine-selective; formycin B serves as a model substrate. Uridine and adenosine are substrates of both systems. Thymidine and cytidine (100 microM), but not formycin B (100 microM) inhibited Na(+)-uridine uptake. In addition, [3H]thymidine exhibited an Na(+)-driven overshoot phenomenon whereas [3H]formycin B did not. Na(+)-thymidine uptake was inhibited by (100 microM) adenosine, uridine, guanosine, but not by formycin B and inosine. Further studies demonstrated that guanosine trans-stimulated thymidine uptake suggesting that guanosine and thymidine share a common transporter in the human renal BBMV. A different pattern was identified in BBMV from the rabbit kidney where both [3H]thymidine and [3H]formycin B as well as [3H]uridine exhibited a transient Na(+)-driven overshoot phenomenon. Collectively, these data suggest that in rabbit renal BBMV both cif and cit systems are present whereas in human renal BBMV, there appears to be a single concentrative Na(+)-nucleoside cotransport system that interacts with uridine, cytidine, thymidine, adenosine and guanosine but not with formycin B and inosine. The system is similar to the previously described cit system except that guanosine is also a substrate.
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