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.
D000818:Animals; D002531:Cerebellum / Q000378:metabolism*; D010134:Fenclonine / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006651:Histocytochemistry; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000096:biosynthesis; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D012701:Serotonin; C001244:6-fluorotryptophan; D014364:Tryptophan; D011433:Propranolol; D014365:Tryptophan Hydroxylase; D007545:Isoproterenol; C006389:N-acetylserotonin; D010134:Fenclonine