TRANSPORT MECHANISMS OF NUCLEOSIDES AND THE DERIVATIVE, 6-MERCAPTOPURINE RIBOSIDE ACROSS RAT 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 inosin e, was recognized by its purine- and pyrimidine-nucleosides transport system, but their nucleo-bases did not entirely inhibit the 6-MPR tran sport. The analysis according to the Hill equation of the curve for 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, an d their affinity constants (K-m value) obtained by Eadie-Hofstee analy sis were approx. 20, 15 and 100 mu M. Moreover, the uptake of radiolab eled adenosine and uridine was trans-stimulated by 6-MPR inside vesicl es in the absence of an inwardly directed Na+-gradient. On the other h and, uridine did not exhibit any inhibitory effects on the uptake of a denosine despite the fact that adenosine was a potent inhibitor for ur idine uptake by intestinal brush-border membrane vesicles. These diffe rences in the inhibition may be explained by the multiplicity of the n ucleoside transport systems.