Transport of 5-fluorouracil and uracil into human erythrocytes

Abstract 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° 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 ( K m 4 mM, V max 500 pmol/sec/5 μ L cells) and nonsaturable (rate constant 80 pmol/sec/mM/5 μ L cells) components of influx. 5-FU, uracil, adenine, and hypoxanthine were competitive inhibitors of each other's influx with K i , values matching their respective K m 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.