The role of L-tryptophan transport in L-tryptophan degradation by indoleamine 2,3-dioxygenase in human placental explants.
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.
Department of Human Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK. yoshiki.kudo@anat.ox.ac.uk
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D000598:Amino Acids, Cyclic / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002824:Chorionic Villi / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D011247:Pregnancy; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000378:metabolism*
D000598:Amino Acids, Cyclic; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase