Retinal melatonin is metabolized within the eye of xenopus laevis

Retinal synthesis of melatonin, a potent modulator of rhythmic retinal processes, is elevated at night as a result of regulation by a circadian clock. Despite high nocturnal synthetic capacity, both melatonin content and release are low in the retina of the frog Xenopus laevis. We report here that cultured eyecups from Xenopus have the capacity for rapid metabolic breakdown of melatonin. Pharmacological analysis indicates that the initial step in this degradation pathway is deacetylation of melatonin by the enzyme aryl acylamidase (aryl-acylamide amidohydrolase, EC 3.5.1.13). This produces 5-methoxytryptamine, which is then deaminated by monoamine oxidase [amine:oxygen oxidoreductase (deaminating) (flavin-containing), EC 1.4.3.4], producing 5-methoxyindoleacetic acid and 5-methoxytryptophol. Inhibition of aryl acylamidase with eserine dramatically increases the release of endogenous melatonin by eyecups cultured at night, indicating that this pathway is the normal fate of retinal melatonin. Metabolism within the eye suggests a local neuromodulatory role for retinal melatonin, in contrast to the hormonal role of pineal melatonin.