Decrease of cerebral serotonin and 5‐hydroxyindolylacetic acid caused by (—)‐α‐methyltryptophan1

TLDR: The effect of AMTP on the concentration of serotonin and its acid metabolite 5H I M (5-hydroxyindolylacetic acid) in the brain is assessed and the availability of the separate isomers of AM TP enabled us to determine the contribution of each to this effect, as well as to other actions of the compound.

Abstract: SINCE 1956 when AMTP (a-methyltryptophan) was shown to stimulate the activity of tryptophan pyrrolase (tryptophan oxygenase; EC 1.13.1.12) in rat liver (SOURKES and TOWNSEND, 1955), this compound has been used in many biochemical experiments on the metabolism of tryptophan. The increased pyrrolase activity evoked by AMTP is analogous to that brought about by the administration of tryptophan (KNOX and MEHLER, 1950) in that it is manifested in adrenalectomized rats (CIVEN and KNOX, 1960) just as in intact animals. However, activation by tryptophan is short-lived, whereas the increased enzymic activity following a single injection of AMTP lasts for many days (SANKOFF and SOURKES, 1962). Chronic elevation of hepatic pyrrolase could lead to a relative deficiency of the indispensable amino acid tryptophan (MADRAS and SOURKES, 1965), and this could affect the formation of important compounds derived from it, namely, tryptamine, serotonin, melatonin and NAD, as well as many proteins. In this paper the effect of AMTP on the concentration of serotonin and its acid metabolite 5H I M (5-hydroxyindolylacetic acid) in the brain is assessed. The availability of the separate isomers of AMTP enabled us to determine the contribution of each to this effect, as well as to other actions of AMTP.