Plasma Total Tryptophan Levels Research Articles

Tryptophan hydroxylase gene ( TPH1) and peripheral tryptophan levels in depression

Background Genetic variants have been discovered in two genes encoding for tryptophan hydroxylase (TPH)— TPH1 and TPH2. Low tryptophan (TRP) levels are associated with depression and may arise because of stress. Evidence suggests that hypothalamic and peripheral 5HT systems have a significant role in appetite regulation, possibly a homeostatic mechanism in regulating peripheral TRP levels. Methods We examined the association between a polymorphism in intron 7 of TPH1, 218A > C and plasma total TRP levels in 118 patients with major depression. Results There was an interaction between 218A > C and gender in determining plasma TRP whereby presence of the 218C allele, in women, was associated with markedly reduced plasma TRP. Limitations The study investigated only the TRP1 gene and did not use a haplotype analysis. The results only apply to a population of subjects suffering from major depression. Conclusions TPH1 may be associated with the regulation of peripheral tryptophan levels and therefore availability of tryptophan to the brain. This may have relevance to a range of neuropsychiatric conditions.

24h withdrawal following repeated administration of caffeine attenuates brain serotonin but not tryptophan in rat brain: Implications for caffeine-induced depression

Caffeine injected at doses of 20, 40 and 80 mg/kg increased brain levels of tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in rat brain. In view of a possible role of 5-HT in caffeine-induced depression the effects of repeated administration of high doses of caffeine on brain 5-HT metabolism are investigated in rats. Caffeine was injected at doses of 80 mg/kg daily for five days. Control animals were injected with sahne daily for five days. On the 6th day caffeine (80 mg/kg) injected to 5 day sahne injected rats increased brain levels of tryptophan, 5-HT and 5-HIAA. Plasma total tryptophan levels were not affected and free tryptophan increased. Brain levels of 5-HT and 5-HIAA but not tryptophan decreased in 5 day caffeine injected rats injected with sahne on the 6th day. Plasma total and free tryptophan were not altered hi these rats. Caffeine-induced increases of brain tryptophan but not 5-HT and 5-HIAA were greater in 5 day caffeine than 5 day sahne injected rats. The findings are discussed as repeated caffeine administration producing adaptive changes in the serotonergic neurons to decrease the conversion of tryptophan to 5-HT and this may precipitate depression particularly in conditions of caffeine withdrawal.

Effect of Tryptophan or Phenobarbital Administration on Hepatic Polyribosomes and Protein Synthesis in Rats Force-Fed a Complete or Threonine-Devoid Diet

Young rats were force-fed a complete or threonine-devoid diet for 3 days. Prior to killing on the fourth morning rats of each group were treated with l-tryptophan (30 mg/100 g body weight) 2 hours before killing or with sodium phenobarbital (8 mg/100 g body weight) 14 hours before killing. Rats force-fed the threonine-devoid diet revealed increased aggregation of polyribosomes (sucrose density gradient analyses) and increased protein synthesis (in vitro [14C]leucine incorporation into protein) in the livers in comparison to that in the livers of rats force-fed the complete diet. Plasma total tryptophan levels were decreased and plasma free tryptophan as a percentage of total plasma tryptophan was increased in rats force-fed the threonine-devoid diet for 3 days. Administration of tryptophan or of phenobarbital stimulated polyribosomal aggregation and in vitro protein synthesis of the livers of rats force-fed the complete or the threonine-devoid diet. These stimulatory effects incuded by tryptophan or phenobarbital were most marked in rats force-fed the threonine-devoid diet. Hepatic tryptophan pyrrolase activity was stimulated to similar degrees following the administration of tryptophan to rats force-fed the complete or the threonine-devoid diet.