Transport of 5-fluorouracil and uracil into human erythrocytes.
The transport of 5-fluorouracil (5-FU) and uracil into human erythrocytes has been investigated under initial velocity conditions with an "inhibitor-stop" assay using a cold papaverine solution to terminate influx. At 37 degrees and pH 7.3, 5-FU influx was nonconcentrative; was partially inhibited by adenine, hypoxanthine, thymine, and uracil; and was insensitive to inhibition by nucleosides or inhibitors of nucleoside transport. Inhibition of the influx of 5-FU or uracil by adenine (3.0 mM) did not increase when other pyrimidines or inhibitors of nucleoside transport were combined with adenine. 5-FU and uracil exhibited similar saturable (Km approximately 4 mM, Vmax approximately 500 pmol/sec/5 microL cells) and nonsaturable (rate constant approximately 80 pmol/sec/mM/5 microL cells) components of influx. 5-FU, uracil, adenine, and hypoxanthine were competitive inhibitors of each other's influx with Ki values matching their respective Km values for influx. We conclude that 5-FU and uracil enter human erythrocytes at similar rates via both nonfacilitated diffusion and the same carrier that transports adenine and hypoxanthine.
Domin
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BA
Division of Experimental Therapy, Wellcome Research Laboratories, Research Triangle Park, NC 27709.
Mahony
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WB
Zimmerman
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D000225:Adenine / Q000378:metabolism; D001692:Biological Transport; D004912:Erythrocytes / Q000378:metabolism*; D005472:Fluorouracil / Q000378:metabolism*; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D007700:Kinetics; D009696:Nucleic Acids / Q000378:metabolism; D009705:Nucleosides / Q000378:metabolism; D010208:Papaverine; D014316:Tritium; D014498:Uracil / Q000378:metabolism*
D007042:Hypoxanthines; D009696:Nucleic Acids; D009705:Nucleosides; D014316:Tritium; D019271:Hypoxanthine; D014498:Uracil; D010208:Papaverine; D000225:Adenine; D005472:Fluorouracil