Dancis J, Lee J, Mendoza S, Liebes L
Department of Pediatrics, Kaplan Cancer Center, New York University School of Medicine, N.Y. 10016.
Placenta. 1993 Sep-Oct;14(5):547-54. doi: 10.1016/s0143-4004(05)80207-3.
Nucleoside transport and metabolism by human placenta was studied using the dual perfusion technique. With [3H] thymidine added to the maternal perfusate and neither perfusate recirculated (steady-state studies) around 40 per cent of the thymidine in the maternal outflow and 50 per cent of the transferred thymidine was degraded. In similar studies with adenosine, over 95 per cent of the nucleoside was degraded. Even with the bolus technique which sharply limits the duration of contact with the placenta, degradation of adenosine was over 95 per cent. Uptake as calculated by the dual-tracer method ([3H] adenosine/[14C] L-glucose) was equally rapid from the maternal and fetal perfusates, was saturable and inhibited by nitrosobenzylthioinosine, consistent with the facilitated diffusion system for nucleosides. Thymidine was taken up at one-third the rate of adenosine. Thymidine in large excess (500 microM) reduced adenosine uptake suggesting a common transporter. Zidovudine, a thymidine analogue used for the treatment of AIDS in which the ribose is modified at the 2' 3' position, did not compete with adenosine for uptake consistent with previous reports that zidovudine is transferred across the placenta by simple diffusion.
采用双重灌注技术研究了人胎盘的核苷转运与代谢。在母体灌注液中加入[3H]胸苷且两种灌注液均不循环（稳态研究）时，母体流出液中约40%的胸苷以及转运的胸苷中有50%被降解。在对腺苷进行的类似研究中，超过95%的核苷被降解。即使采用能大幅缩短与胎盘接触时间的推注技术，腺苷的降解率仍超过95%。通过双示踪法（[3H]腺苷/[14C] L-葡萄糖）计算得出的摄取量，在母体和胎儿灌注液中同样迅速，具有饱和性且受到亚硝基苄基硫代肌苷的抑制，这与核苷的易化扩散系统一致。胸苷的摄取速率是腺苷的三分之一。大量过量的胸苷（500 microM）会降低腺苷的摄取，提示存在一种共同转运体。齐多夫定是一种用于治疗艾滋病的胸苷类似物，其核糖在2' 3' 位置被修饰，它不会与腺苷竞争摄取，这与之前关于齐多夫定通过简单扩散穿过胎盘的报道一致。
