Inhibition of uridine transport in cultured mammalian cells by theophylline.
Theophylline (theobromine, caffeine) reversibly inhibits the incorporation of labeled RNA precursors both in confluent 37 RC and in exponentially growing HeLa cells. As measured in 37 RC after 2 h labeling, 20 mM theophylline reduces the incorporation of [3H]UTP and [14C]uridine into acid-precipitable material to 5% and 9% of the control, respectively. This reduction is paralleled by a comparably lowered incorporation of the same precursors into the acid-soluble pool. The initial rate of incorporation into total cell material is similarly affected by theophylline, the inhibition being of a simple competitive type. Theophylline does not alter the turnover rate of pulse labeled RNA during actinomycin D chase nor does it preclude the utilization of the endogenous pool of nucleoside phosphates. Upto a concentration of 10 mM, it does not inhibit uridine kinase neither in 37 RC nor in HeLa cells. The mentioned inhibitory effects of theophylline cannot be mimicked by exogenously added cyclic AMP. All the data support the conclusion that theophylline inhibits the transport of uridine into the cell.
Benedetto
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Centre of Virology, O.O.R.R., Rome, Italy.
Cassone
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D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D012313:RNA / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology*; D014316:Tritium; D014529:Uridine / Q000378:metabolism*; D014541:Uridine Kinase / Q000378:metabolism; D014544:Uridine Triphosphate / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology
D012322:RNA Precursors; D014970:Xanthines; D014316:Tritium; C008514:methylxanthine; D012313:RNA; D013806:Theophylline; D014541:Uridine Kinase; D014544:Uridine Triphosphate; D014529:Uridine