MELATONIN: DEACETYLATION TO 5-METHOXYTRYPTAMINE BY LIVER BUT NOT BRAIN ARYL ACYLAMIDASE |
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Authors: | Michael A. Rogawski Robert H. Roth George K. Aghajanian |
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Affiliation: | Departments of Pharmacology and Psychiatry, Yale University School of Medicine and the Connecticut Mental Health Center, New Haven, CT 06510, U.S.A. |
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Abstract: | Abstract— Rat liver and brain slices were incubated in vitro with [3H]melatonin. Liver slices synthesized small amounts of [3H]5-methoxyindoleacetic acid ([3H]5-MIAA) along with other melatonin metabolites including 6-hydroxymelatonin. Pretreatment of animals prior to killing with the irreversible monoamine oxidase inhibitor pargyline allowed [3H]5-methoxytryptamine ([3H]5-MT) to be recovered from the incubation. No [3H]5-MIAA or [3H]5-MT could be detected in incubations with hypothalamic slices or following intraventrieular injection of [3H]melatonin. The possibility that the deacetylase aryl acylamidase was in part responsible for the deacetylation occurring in liver slices was examined. Liver aryl acylamidase was able to utilize [3H]melatonin as substrate to produce [3H]5-MT. Furthermore, the liver enzyme was inhibited by melatonin ( Ki. 1 m m ) when tested with the alternate substrate o -nitroacetanalide. Brain aryl acylamidase did not generate any detectable [3H]5-MT nor was it inhibited by melatonin. These results suggest that 5-MT is not formed in brain from melatonin although trace amounts of 5-MT in the periphery could be derived from this precursor. |
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