色氨酸负荷期间大脑犬尿氨酸和5-羟色胺途径的调节

Regulation of cerebral kynurenine and 5-hydroxyindole pathways during tryptophan loading.

作者信息

Rizza V, Bousquet E, Guerrera F, De Regis M

出版信息

Cephalalgia. 1983 Aug;3 Suppl 1:139-42. doi: 10.1177/03331024830030S121.

Abstract

Cerebral tryptophan metabolism was studied in rat brain slices. The results show that serotonin production was inhibited at high levels of tryptophan or 5-oxo-L-prolyltryptophan. In contrast, kynurenine formation showed a dose dependent increase at the various concentrations of tryptophan or 5-oxo-L-prolyltryptophan. Measurements of the activities of tryptophan hydroxylase (TH) and indoleamine 2,3-dioxygenase (IDOase) in crude brain homogenates showed that serotonin formation was linear in the presence of dithiothreitol, whereas kynurenine production was inhibited in the presence of dithiothreitol or superoxide dismutase. These results suggest an inverse relationship in the regulation of 5-hydroxyindole and kynurenine pathways. The former being inhibited in the presence of high tryptophan concentration while the latter is enhanced. Furthermore, a high intracellular thiol-disulphide ratio appears to favour serotonin formation, whereas a highly reducing environment decreases kynurenine production.

摘要

在大鼠脑片中研究了脑内色氨酸代谢。结果表明，在色氨酸或5-氧代-L-脯氨酰色氨酸水平较高时，5-羟色胺的生成受到抑制。相反，在色氨酸或5-氧代-L-脯氨酰色氨酸的不同浓度下，犬尿氨酸的形成呈剂量依赖性增加。对粗脑匀浆中色氨酸羟化酶（TH）和吲哚胺2,3-双加氧酶（IDOase）活性的测量表明，在二硫苏糖醇存在下，5-羟色胺的形成呈线性，而在二硫苏糖醇或超氧化物歧化酶存在下，犬尿氨酸的生成受到抑制。这些结果表明在5-羟吲哚和犬尿氨酸途径的调节中存在反比关系。前者在色氨酸浓度高时受到抑制，而后者则增强。此外，较高的细胞内硫醇-二硫键比例似乎有利于5-羟色胺的形成，而高度还原的环境会减少犬尿氨酸的生成。