The role of L-tryptophan transport in L-tryptophan degradation by indoleamine 2,3-dioxygenase in human placental explants

被引:50
作者
Kudo, Y [1 ]
Boyd, CAR [1 ]
机构
[1] Univ Oxford, Dept Human Anat & Genet, Oxford OX1 3QX, England
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2001年 / 531卷 / 02期
关键词
D O I
10.1111/j.1469-7793.2001.0417i.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. The physiological importance of L-tryptophan transport for placental indoleamine 2,3-dioxygenase-mediated degradation of L-tryptophan has been studied using human placental chorionic villous explants. 2. L-Tryptophan influx into villous explants is supported exclusively by transport system L and is substantially inhibited by the L-system-specific substrate 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) and also by I-methyl-tryptophan which is also an inhibitor of indoleamine 2,3-dioxygenase. L-Tryptophan influx is enhanced 2.3-fold following in vitro culture of the villous explant. Interferon-gamma, which increases villous explant indoleamine 2,3-dioxygenase expression, has no effect on L-tryptophan influx. 3. In explants both BCH and 1-methyl-tryptophan inhibit indoleamine 2,3-dioxygenase-mediated L-tryptophan degradation. This also applies when L-tryptophan degradation has been stimulated by interferon-gamma. 4, These findings show transport of L-tryptophan into the trophoblast to be a rate-limiting step for indoleamine 2,3-dioxygenase-mediated L-tryptophan degradation and therefore for the normal physiology of mammalian pregnancy.
引用
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页码:417 / 423
页数:7
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