Nakamura T, Shinno H, Ichihara A
J Biol Chem. 1980 Aug 25;255(16):7533-5.
The basal activity of tryptophan 2,3-dioxygenase (EC-1.13.11.11) in primary cultured rat hepatocytes decreased during culture, but addition of either tryptophan (2.5 x 10(-3) M) or dexamethasone (1 x 10(-6) M) could prevent the decrease. Addition of both compounds caused severalfold induction of activity. Glucagon (1 x 10(-8) M) alone did not induce the activity, but its inductive effect in combination with tryptophan was similar to that of tryptophan plus dexamethasone. The effect of glucagon was additive with those of tryptophan and dexamethasone and hence the highest induction (7-fold) was achieved by addition of all three inducers. Glucagon could be replaced by dibutyryl cyclic AMP (1 x 10(-5) M). Insulin (1 x 10(-8) M) inhibited the inductions by glucagon and dexamethasone, but not that by tryptophan. Cycloheximide inhibited the inductions by all three inducers, but actinomycin D inhibited only the induction by dexamethasone. These results suggest that the three compounds have different mechanisms of induction of tryptophan oxygenase activity: tryptophan prevents enzyme inactivation, dexamethasone may stimulate enzyme synthesis at the level of transcription, and glucagon may enhance the synthesis at the translational level.
原代培养的大鼠肝细胞中色氨酸2,3 -双加氧酶（EC - 1.13.11.11）的基础活性在培养过程中下降，但添加色氨酸（2.5×10⁻³ M）或地塞米松（1×10⁻⁶ M）均可防止其下降。同时添加这两种化合物会使活性诱导增加数倍。单独的胰高血糖素（1×10⁻⁸ M）不会诱导该活性，但其与色氨酸联合的诱导作用与色氨酸加地塞米松的诱导作用相似。胰高血糖素的作用与色氨酸和地塞米松的作用具有加和性，因此同时添加所有三种诱导剂可实现最高诱导（7倍）。胰高血糖素可用二丁酰环磷腺苷（1×10⁻⁵ M）替代。胰岛素（1×10⁻⁸ M）抑制胰高血糖素和地塞米松的诱导作用，但不抑制色氨酸的诱导作用。放线菌酮抑制所有三种诱导剂的诱导作用，但放线菌素D仅抑制地塞米松的诱导作用。这些结果表明，这三种化合物诱导色氨酸加氧酶活性的机制不同：色氨酸防止酶失活，地塞米松可能在转录水平刺激酶合成，而胰高血糖素可能在翻译水平增强合成。
