DL-α-Methyltryptophan

1. In agreement with previous findings on whole brain, the intraperitoneal injection of hydrocortisone, DL-alpha-methyltryptophan or L-kynurenine decreased the concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxy-indoleacetic acid (5-HIAA) in different regions of the rat brain.2. Hydrocortisone caused similar decreases in the concentrations of both 5-HT and 5-HIAA, suggesting decreased 5-HT synthesis.3. Changes in the concentration of 5-HIAA after hydrocortisone corresponded significantly to those after alpha-methyltryptophan. Changes in the concentration of 5-HT did not correspond, possibly due to falsely high 5-HT values because of interfering material derived from alpha-methyltryptophan.4. In general, kynurenine caused larger decreases in the concentration of 5-HT than in the concentration of 5-HIAA.5. In agreement with previous findings with whole brain, immobilization of rats for 5 h decreased the concentration of 5-HT and increased that of 5-HIAA in most brain regions.6. The order of the percentage decreases in the concentrations of 5-HIAA 6 h after hydrocortisone injection was, in decreasing order: hypothalamus, striatum, cerebellum, mid-brain, pons + medulla and cortex. The percentage increases after immobilization for 5 h were in the reverse order.7. The differences between the percentage decreases in the concentration of 5-HIAA after hydrocortisone and the percentage increases after immobilization were very similar in all regions except the hypothalamus. This is consistent with immobilization stress increasing the firing rate of 5-hydroxytryptaminergic neurones similarly in different regions.8. During the first 3 h of immobilization the concentrations of 5-HIAA in the hypothalamus and in the rest of the brain increased approximately in parallel. Between 3 and 5 h, 5-HIAA returned to control concentrations in the hypothalamus while continuing to rise in the rest of the brain.9. Relative changes in the concentration of 5-HT in particulate and supernatant fractions after the various treatments were comparable except 2 h after kynurenine injection when the concentration 5-HT fell in the particulate but not in the supernatant fraction. The concentration of 5-HT did fall in the latter, though more slowly than in the former fraction, suggesting a concentration of amine synthesizing organelles in particulate material.

DL-alpha-Methyltryptophan (alphaMeTrp), a synthetic analogue of tryptophan, has been found to be a potent inducer of hepatic tyrosine aminotransferase activity in the adrenalectomized rat. alphaMeTrp is inactive in vitro. Unlike the action of other known inducers (tryptophan, hydrocortisone, adenosine cyclic 3:5-monophosphate, and glucagon), maximal stimulation of enzyme activity occurs only 16 to 30 hours after alphaMeTrp administration and the activity is still elevated at 96 hours. Only the L isomer of alphaMeTrp is active, and addition of a hydroxyl group to position 5 of the indole ring renders an inactive compound. The induction can be prevented by actinomycin D or cycloheximide but not galactosamine. Administration of alphaMeTrp together with hydrocortisone produced an additive stimulation of enzyme activity. alphaMeTrp given along with glucagon or adenosine cyclic 3:5-monophosphate caused a further but not additive increase in enzyme activity. Tryptophan given along with alphaMeTrp promoted no extra stimulation whatsoever. These data indicate that alphaMeTrp and tryptophan may act via a common pathway which in part requires RNA synthesis. Other enzymes, namely alanine and aspartate aminotransferase, ornithine aminotransferase, ornithine carbamoyltransferase, serine dehydratase, and histidine ammonialyase, were not affected by treatment of rats with alphaMeTrp.