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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Renal organic cation and nucleoside transport.

We previously reported that the rat organic cation transporter rOCT1 could transport the nucleoside analog deoxytubercidin (dTub) (Chen R, Nelson JA. Biochem Pharmacol 2000;60:215-9). The cationic form of dTub (dTub(+)) appeared to be the true substrate of rOCT1. We also reported that although rOCT2 is similar to rOCT1, it does not transport dTub at pH 7. 4. In this study, we measured the K(m) and V(max) values of dTub(+) uptake at a reduced pH (pH 5.4) for both rOCT1 and rOCT2. The difference in substrate activity appears due, in large part, to a poor affinity of rOCT2 for dTub(+). The transport efficiency estimated by V(max)/K(m) values for rOCT2 was only 6% that of rOCT1. Chimeras constructed between rOCT1 and rOCT2 revealed that the difference in dTub binding lies within transmembrane domains 2-7. To evaluate the potential of OCT1 in the renal secretion of dTub, tissue distribution and urinary excretion of dTub in OCT1 knockout mice were measured. No significant difference was observed in renal elimination, plasma level, and tissue distribution of dTub between the knockout and the wild-type mice. Therefore, dTub is a good substrate for OCT1; however, OCT1 does not appear to be necessary for its renal secretion.[1]


  1. Renal organic cation and nucleoside transport. Chen, R., Jonker, J.W., Nelson, J.A. Biochem. Pharmacol. (2002) [Pubmed]
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