Transport mechanisms of nucleosides and the derivative, 6-mercaptopurine riboside across rate intestinal brush-border membranes.

Na+ -driven nucleoside transport processes across rat intestinal brush-border membrane vesicles were investigated. 6-Mercaptopurine riboside (6-MPR), an analogue of purine-nucleoside such as adenosine and inosine, was recognized by its purine- and pyrimidine-nucleosides transport system, but their nucleobases did not entirely inhibit the 6-MPR transport. The analysis according to the Hill equation of the curve of Na+ activation of 6-MPR uptake was consistent with the notion of a Na+/6-MPR coupling stoichiometry of 1:1. The expressed transport activities of adenosine, uridine, and 6-MPR were Na+ -dependent and saturable, and their affinity constants (Km value) obtained by Eadie-Hofstee analysis were approx. 20, 15 and 100 microM. Moreover, the uptake of radiolabeled adenosine and uridine was trans-stimulated by 6-MPR inside vesicles in the absence of an inwardly directed Na+ gradient. On the other hand, uridine did not exhibit any inhibitory effects on the uptake of adenosine despite the fact that adenosine was a potent inhibitor of uridine uptake by intestinal brush-border membrane vesicles. These differences in the inhibition may be explained by the multiplicity of the nucleoside transport systems.