Gati W P, Knaus E E, Wiebe L I
Mol Pharmacol. 1983 Jan;23(1):146-52.
The efflux of radioactive thymidine from human erythrocytes at 25 degrees was accelerated in the presence of extracellular 2'-fluoro-2'-deoxyuridine to a maximal velocity 120% of that observed in the presence of extracellular nonradioactive thymidine. Efflux in the presence of 2'-chloro-2'-deoxyuridine and 2'-bromo-2'-deoxyuridine did not exceed 56% and 49%, respectively. 2'-Iodo-2'-deoxyuridine did not accelerate thymidine efflux. In comparison, 2'-fluoro-2'-deoxycytidine and 2'-deoxyuridine accelerated thymidine efflux to maximal velocities of 170% and 91%, respectively. The half-saturation constant for acceleration of thymidine efflux by 2'-fluoro-2'-deoxycytidine was higher (0.90 mM) than those estimated for the other substances (0.22 mM or lower). Influx competition experiments at 25 degrees showed that all of the above nucleosides competitively inhibited influx of thymidine into human erythrocytes. The Km for the zero-trans influx of thymidine was 0.051 +/- 0.008 mM, while the Ki values for 2'-deoxyuridine and the 2'-halogeno-2'-deoxyuridines were similar, ranging from 0.04 to 0.09 mM. The Ki for 2'-fluoro-2'-deoxycytidine was 0.18 mM. These results suggest that, although all nucleosides tested appeared to bind to the same transport site on the external membrane surface, their ease of transport through the membrane was determined by the properties of the halogen substituent at position 2'.
在25摄氏度下，细胞外2'-氟-2'-脱氧尿苷存在时，人红细胞中放射性胸苷的流出速度加快，最大速度为细胞外非放射性胸苷存在时观察到的120%。2'-氯-2'-脱氧尿苷和2'-溴-2'-脱氧尿苷存在时的流出速度分别不超过56%和49%。2'-碘-2'-脱氧尿苷不会加快胸苷流出。相比之下，2'-氟-2'-脱氧胞苷和2'-脱氧尿苷分别将胸苷流出速度加快到最大速度的170%和91%。2'-氟-2'-脱氧胞苷加速胸苷流出的半饱和常数（0.90 mM）高于其他物质估计的半饱和常数（0.22 mM或更低）。25摄氏度下的流入竞争实验表明，上述所有核苷都竞争性抑制胸苷流入人红细胞。胸苷零转运流入的Km为0.051±0.008 mM，而2'-脱氧尿苷和2'-卤代-2'-脱氧尿苷的Ki值相似，范围为0.04至0.09 mM。2'-氟-2'-脱氧胞苷的Ki为0.18 mM。这些结果表明，尽管所有测试的核苷似乎都与外膜表面的同一转运位点结合，但其通过膜的转运难易程度由2'位卤素取代基的性质决定。
