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-thiazolecarboxylic acid (TEI-6720), an inhibitor of xanthine oxidase, on purine metabolism in the lung cancer cell line A549, the activities of adenosine deaminase, purine nucleoside phosphorylase, adenine phosphoribosyltransferase, hypoxanthine guanine phosphoribosyltransferase, xanthine oxidase, and guanase together with pyrimidine nucleoside phosphorylase were measured with or without the addition of TEI-6720, and the extracellular concentrations of hypoxanthine, 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 xanthine oxidase in A549 cells, but did not affect other enzymes. During incubation, TEI-6720 not only prevented a decrease in the inosine concentration in inosine-containing medium, but also a decrease in the uridine concentration in uridine-containing medium. Furthermore, the Na-independent transport of uridine was inhibited by TEI-6720 with a K(i) value of 4.1 micromol/l. These results indicate that TEI-6720 is an inhibitor of the Na-independent nucleoside transport of uridine and inosine, as well as xanthine oxidase.
Yamamoto
T
T
3rd Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Moriwaki
Y
Y
Fujimura
Y
Y
Takahashi
S
S
Tsutsumi
Z
Z
Tsutsui
T
T
Higashino
K
K
Hada
T
T
D000493:Allopurinol / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000069465:Febuxostat; D006801:Humans; D019271:Hypoxanthine / Q000494:pharmacology; D007288:Inosine / Q000494:pharmacology; D008175:Lung Neoplasms; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D033703:Nucleoside Transport Proteins; D009705:Nucleosides / Q000378:metabolism*; D010430:Pentosyltransferases / Q000378:metabolism; D011687:Purines / Q000737:chemistry / Q000378:metabolism; D057845:Pyrimidine Phosphorylases; D013844:Thiazoles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014498:Uracil / Q000378:metabolism; D014529:Uridine / Q000378:metabolism / Q000494:pharmacology; D019820:Xanthine / Q000378:metabolism; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D033703:Nucleoside Transport Proteins; D009705:Nucleosides; D011687:Purines; D013844:Thiazoles; D000069465:Febuxostat; D019820:Xanthine; D019271:Hypoxanthine; D014498:Uracil; D007288:Inosine; D000493:Allopurinol; D014969:Xanthine Oxidase; D010430:Pentosyltransferases; D057845:Pyrimidine Phosphorylases; D014529:Uridine