B-adrenergic regulation of N-acetylserotonin (NAS) synthesis in the rat cerebellum.

The synthesis of N-acetylserotonin (NAS) in the pineal gland is dependent upon the activity of the enzymes tryptophan-hydroxylase, 1-aromatic amino acid decarboxylase and N-acetyltransferase. Pineal N-acetyltransferase activity is regulated by the level of B-adrenergic activation. N-acetylserotonin (NAS) has also been identified in extra-pineal brain tissue. In order to investigate whether extra-pineal brain NAS levels are regulated by tryptophan hydroxylase and B-adrenergic activity, the effects of tryptophan hydroxylase inhibitors (parachlorophenylalanine and 6-fluoro-tryptophan) and adrenergic drugs (l-isoproterenol and propranolol) were examined. NAS was evaluated in the cerebellum of the rat using quantitative NAS-immunohistochemistry. A significant decrease in NAS-immunofluorescence was observed after tryptophan hydroxylase inhibition. Treatment with l-isoproterenol, a B-adrenergic agonist, resulted in a significant increase in NAS-immunofluorescence intensity. This effect was blocked by propranolol, a B-adrenergic blocking agent. These data indicate that the synthesis of NAS, in the cerebellum utilizes the established serotonin pathway and that NAS synthesis in the cerebellum is regulated by a B-adrenergic mechanism similar to that in the pineal gland.