d-Aspartate modulates melatonin synthesis in rat pinealocytes

It has been known that pinealocytes contain the highest level of d-aspartate among various neuroendocrine cells in the rat. Here, we report that exogenous d-aspartate strongly inhibited norepinephrine-dependent melatonin synthesis in the rat pineal gland, the concentration required for 50% inhibition being 75 μM. This inhibition was due at least partly to decreased norepinephrine-dependent serotonin N-acetyltransferase activity. Upon incubation, d-aspartate was gradually released from pinealocytes and accumulated in the incubation medium as determined by high-performance liquid chromatography on a Pirkle-type chiral column. These results suggest that d-aspartate acts as a negative regulator for melatonin synthesis in the pineal gland.