Effect of inosine on the plasma concentration of uridine and purine bases.
To examine whether inosine increases the plasma concentration of uridine, 20 mg/kg body weight of inosine was orally administered to 5 healthy subjects. The plasma concentration of uridine was increased by 1.25-fold (P <.05), while that of hypoxanthine, xanthine, and uric acid was increased by 1.26-fold (P <.01), 1.26-fold (P <.01), and 1.2-fold (P <.05), respectively, 2.5 hours after the oral administration of inosine. In addition, the 1-hour urinary excretion of uridine was increased by 1.17-fold (P <.05) and that of hypoxanthine, xanthine, and uric acid by 1.38-fold (P <.05), 1.4-fold (P <.05), and 1.4-fold (P <.05) between 2 and 3 hours after the administration of inosine. We also conducted an in vitro study with Mahlavu cells and found that the addition of inosine (50 micromol/L) inhibited a decrease in the concentration of uridine in medium originally containing 50 micromol/L uridine. Further, we demonstrated that the apparent Km and Vmax values for Na-independent uridine transport were 67.0 +/- 4.3 micromol/L and 7.0 +/- 0.3 pmol/mg protein/s, respectively, and the Ki value of inosine for Na-independent uridine transport was 45.1 +/- 12.1 micromol/L. These results suggest that inosine inhibits uridine uptake via the nucleoside transport pathway, and administered inosine is converted to purine bases (uric acid, hypoxanthine, and xanthine) in the intestine and liver, before entering the systemic circulation via the hepatic vein.
Yamamoto
Tetsuya
T
Third Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Moriwaki
Yuji
Y
Cheng
Jidong
J
Takahashi
Sumio
S
Tsutsumi
Zenta
Z
Ka
Tuneyoshi
T
Hada
Toshikazu
T
D000328:Adult; D006528:Carcinoma, Hepatocellular; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019271:Hypoxanthine / Q000097:blood*; D007288:Inosine / Q000097:blood* / Q000494:pharmacology*; D007700:Kinetics; D008113:Liver Neoplasms; D011687:Purines / Q000097:blood*; D012016:Reference Values; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014527:Uric Acid / Q000097:blood*; D014529:Uridine / Q000097:blood*; D019820:Xanthine / Q000097:blood*
D011687:Purines; D019820:Xanthine; D014527:Uric Acid; D019271:Hypoxanthine; D007288:Inosine; D003404:Creatinine; D014529:Uridine