Tryptophan Administration Inhibits Nocturnal N-Acetyltransferase Activity and Melatonin Content in the Rat Pineal Gland

Abstract

In the rat pineal gland, the activity of serotonin N-acetyltransferase (NAT) and the concentration of melatonin are normally high at night; conversely, the concentration of serotonin (5-HT), the precursor of melatonin, is low. Since tryptophan administration increases the concentration of pineal 5-HT at night, we examined its effect of melatonin production. Nighttime tryptophan loading led to substantial increases in pineal 5-hydroxytryptophan, 5-hydroxyindole acetic acid (5-HIAA), and 5-HT but a highly significant reduction in NAT activity in comparison to saline-injected controls. In contrast to other measured indoles, melatonin levels also were significantly diminished by tryptophan loading. Nocturnally high pineal norepinephrine levels were unaltered by tryptophan administration. The idea that high concentrations of 5-HT could lead to substrate inhibition of NAT activity was not supported by kinetic analysis of control NAT levels versus tryptophan-inhibited NAT activity under varied substrate concentrations. Hypotheses to explain these results include the possibility that tryptophan inhibition of melatonin synthesis is mediated by the release of 5-HT from the pinealocyte and its subsequent autocrine action on melatonin production.

Partial characterization of serotonin N - acetyltransferases from northern pike (Esox lucius, L. pineal organ and retina: effects of temperature

“…The apparent of Km values for acetyl-CoA, observed in the pike pineal organ and retina, were within the range of those previously reported for mammals [18,24,35]. However, in the pike, affinity for the acetyl donor appeared higher for retinal than for pineal organ NAT.…”

Nocturnal plasma levels of melatonin in quails (Coturnix japonica) injected with l-5-hydroxy-tryptophan

“…Similar observations to ours were made by Reiter et al (1990), who noted an increase in the glandular content of L-HTP, 5-HT and acid 5-hydroxy-indol acetic (5-HIAA) after nocturnal overload of L-TRP in rats. The authors attributed this observation to autocrine serotonin action (derived from an increase of the precursor availability) that would act in the pinealocytes, inhibiting melatonin synthesis.…”

“…Alternatively, instead of autocrine action, the serotonin-originated mechanism could be worked from serotoninergic neurons of the midbrain raphe (Matsuura and Sano, 1983;Leander et al, 1998). Therefore, serotonin synthesized from L-HTP administration and released in synapses in the pineal could be the mediator of the responses described by Reiter et al (1990). If this hypothesis is correct, the serotoninergic output relayed from the midbrain raphe towards the pineal could constitute a nocturnal mechanism of modulation of NAT activity and therefore, of melatonin synthesis.…”

“…TPO is considered the rate-limiting enzyme of the serotonin synthesis in serotoninergic neurons (Tyce, 1990;Boadle-Biber, 1993). Administration of serotonin precursors (and thus leading to melatonin synthesis) has given rise to controversial results (Namboodiri et al, 1983;Sugden et al, 1985;Cavallo et al, 1987;Reiter et al, 1990;McIntyre and Oxenkrug, 1991;Nathan et al, 1998;Steardo et al, 2000;Huether et al, 1993). However, such a model has not been employed in birds to evaluate the effect of brain serotonin precursors on melatonin synthesis.…”

Circannual Analysis of Pineal Gland Indoles and Vasotocin-Like Immunoreactivity in Male Rats Kept on Constant Photoschedules and Temperature

“…The increase in 5HT levels may have resulted from increased substrate availability of the amino acid tryp tophan, because circannual changes in pineal tryptophan exhibited a close phase relation ship with the rhythm in 5HT. In the rat pineal gland, tryptophan administration resulted in increased levels of 5HT [35].…”