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

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Abstract
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 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-γ, 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-γ. 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.

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