Uptake of 6‐Mercaptopurine Riboside via the Nucleoside Transporter in the Human Intestinal Brush‐border Membrane

Abstract

The transport systems of 6-mercaptopurine riboside (6-MPR), a nucleoside analogue, in the human jejunal brush-border membrane and in the human epithelial cell line, Caco-2, were investigated. The transport activities of 6-MPR were found to be dependent upon an inward Na+-gradient at pH 5·5. Trans-stimulation studies indicated that the uptakes of both [3H]adenosine and [3H]uridine were significantly increased by the presence of 6-MPR inside the human brush-border membrane vesicles. The uptake of 6-MPR from the apical side of Caco-2 monolayer was sensitive for an inward-directed Na+-gradient, and a greater uptake was observed at an acidic medium (pH 5·5>7·5). Moreover, both adenosine and uridine were significantly effective in inhibiting the 6-MPR uptake by Caco-2. These results indicate that an analogue of adenosine, 6-MPR, is able to be taken up via the Na+-gradient-dependent purine- and pyrimidine-nucleosides transport systems in the human intestinal brush-border membrane.