Effect of TEI-6720, a xanthine oxidase inhibitor, on the nucleoside transport in the lung cancer cell line A549

To examine the effect of 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolec arboxylic acid (TEI-6720), an inhibitor of xanthine oxidase, on purine meta bolism in the lung cancer cell line A549, the activities of adenosine deami nase, purine nucleoside phosphorylase, adenine phosphoribosyltransferase, h ypoxanthine guanine phosphoribosyltransferase, xanthine oxidase, and guanas e together with pyrimidine nucleoside phosphorylase were measured with or w ithout the addition of TEI-6720, and the extracellular concentrations of hy poxanthine, xanthine, inosine, uracil, and uridine were measured after the addition of inosine or uridine to the incubation medium with or without TEI -6720. Moreover, the Na-independent nucleoside transport was determined in A549 cells with or without TEI-6720. TEI-6720 inhibited the activity of xan thine oxidase in A549 cells, but did not affect other enzymes. During incub ation, TEI-6720 not only prevented a decrease in the inosine concentration in inosine-containing medium, but also a decrease in the uridine concentrat ion in uridine-containing medium. Furthermore, the Na-independent transport of uridine was inhibited by TEI-6720 with a Ki value of 4.1 mu mol/l. Thes e results indicate that TEI-6720 is an inhibitor of the Na-independent nucl eoside transport of uridine and inosine, as well as xanthine oxidase. Copyr ight (C) 2000 S. Karger AG, Basel.