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

J Physiol. 2001 Mar 1;531(Pt 2):417-23. doi: 10.1111/j.1469-7793.2001.0417i.x.


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. 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 1-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. 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. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids, Cyclic / pharmacology
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Chorionic Villi / metabolism*
  • Female
  • Humans
  • In Vitro Techniques
  • Interferon-gamma / pharmacology
  • Pregnancy
  • Tryptophan / analogs & derivatives*
  • Tryptophan / antagonists & inhibitors
  • Tryptophan / metabolism*
  • Tryptophan / pharmacology
  • Tryptophan Oxygenase / metabolism*


  • Amino Acids, Cyclic
  • 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid
  • Interferon-gamma
  • Tryptophan
  • Tryptophan Oxygenase