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Circadian Regulation of Melatonin in the Retina of Xenopus laevis: Limitation by Serotonin Availability
Author(s) -
Cahill Gregory M.,
Besharse Joseph C.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb01932.x
Subject(s) - melatonin , serotonin , circadian rhythm , medicine , endocrinology , tryptophan , pargyline , biology , xenopus , tryptophan hydroxylase , serotonergic , darkness , monoamine oxidase inhibitor , retinal , monoamine oxidase , biochemistry , receptor , enzyme , botany , amino acid , gene
Treatments expected to increase retinal serotonin levels were found to stimulate melatonin production by cultured eyecups from Xenopus laevis. The monoamine oxidase inhibitor pargyline (100 μM ) caused a sixfold increase in melatonin release, and the serotonin precursor 5‐hydroxy‐L‐tryptophan (100 μM ) caused a 70‐fold increase. Both acted synergistically with eserine, an inhibitor of melatonin deacetylation in the retina. The effect of 5‐hydroxytryptophan was dose dependent, with effects increasing from 1 to 100 μM . Increasing the tryptophan level in the culture medium had no effect on melatonin release. These results indicate that the rate‐limiting step in retinal melatonin synthesis is 5‐hydroxylation of tryptophan. Melatonin released from individual eyecups in superfusion culture in constant darkness with and without added 5‐hydroxy‐L‐tryptophan was monitored over a 5‐day period. Control eyecups released low levels of melatonin, with circadian rhythmicity persisting for 1–3 days. With 5‐hydroxy‐L‐tryptophan added, melatonin levels were elevated 10–20‐fold at all times, and rhythmicity was apparent for as long as five cycles. This provides a model system for studies of the circadian clock in the eye.