Abstract
The synthesis of N-acetylserotonin (NAS) in the pineal gland is dependent upon the activity of the enzymes tryptophan-hydroxylase, l-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 extrapineal brain tissue. In order to investigate whether extrapineal brain NAS levels are regulated by tryptophan hydroxylase and B-adrenergic activity, the effects of tryptophan hydroxylase inhibitors (parachlorophenylalanine and 6-fluorotryptophan) 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 decrease in NAS-immunofluorescence intensity. This effect was blocked by propanolol, 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.
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