N6-(delta2-isopentenyl)adenosine, an inhibitor of cellular transport of uridine and cytidine

Journal of Cellular Physiology
M T HakalaG J Gryko

Abstract

N6-(delta2-Isopentenyl)adenosine (IPAR) inhibited severely the incorporation of uridine and cytidine into S-180 cells in culture. When IPAR and the nucleosides were simultaneously present in the medium the inhibition was competitive (Ki 3.4 muM) and indicated inhibition of transport. However, the inhibition occurred even in the absence of extracellular IPAR if the cells had been preincubated with IPAR. Since 5'-IPAMP was the product which accumulated in large quantities in S-180 cells when incubated with IPAR, the effects of this AMP analog of the intracellular metabolism of uridine had to be considered. No direct correlation between the amount of intracellular IPAMP and the degree of inhibition of uridine utilization was observed and the relative distribution of uridine nucleotides in the acid soluble pool of the cells was unaltered in cells treated with IPAR. Also, IPAMP was not an inhibitor of uridine kinase in a cell free system nor was the activity of this enzyme affected by treatment of cells with IPAR. In addition, a profound inhibition of uridine utilization was also observed in a resistant subline of S-180 cells, which is unable to form IPAMP. These data suggest that IPAMP was not the inhibitory agent. Furthermore, the...Continue Reading

References

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Citations

Jan 1, 1976·Advances in Enzyme Regulation·Y M RustumE Mihich
Jan 7, 2009·International Journal of Cancer. Journal International Du Cancer·Francesca ColomboTommaso A Dragani
Jun 5, 2021·Nature Communications·Malina A BakowskiThomas F Rogers
Jan 22, 2011·Chemical Reviews·Lan Lin, Ren Xiang Tan

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