Differential effects of indolepyruvic acid and 5-hydroxytryptophan on indole metabolism in the pineal gland of the rat during the light-dark cycle.

The effect of two serotonin precursors, 5-hydroxytryptophan (5-OH-TRP) and indolepyruvic acid (IPA), a tryptophan ketoanalogue, on rat pineal indole metabolism during the light-dark cycle was investigated. 5-OH-TRP drastically increased the production of 5-hydroxyindoleacetic acid at a dose of only 10 mg/kg, whereas 50-100 mg/kg was needed to reach higher serotonin levels. It had no effect on the pathway leading to the production of N-acetylserotonin and melatonin. IPA, on the other hand, led to a marked dose-related increase in tryptophan, 5-OH-TRP, serotonin and 5-OH-indoleacetic acid, and was also active on N-acetylserotonin and melatonin synthesis in both phases. The different behaviour of these two substances with regard to melatonin synthesis was also confirmed by their effects on N-acetyltransferase, since IPA increased, whereas 5-OH-TRP decreased its activity. These data suggest that an increase in serotonin does not necessarily lead to an increase in melatonin, and that IPA may in fact induce this effect by altering the activity on N-acetyltransferase, which is regarded as a key enzyme in pineal hormone synthesis.