RhythmsElevation of melatonin in chicken retina by 5-hydroxytryptophan: differential light/dark responsesThomas, K Bradford1; Brown, Audra D.1; Iuvone, P Michael1,2Author Information 1Department of Pharmacology, 1510 Clifton Rd, Emory University, Atlanta, GA 30322-3090, USA 2Corresponding Author: P. Michael Iuvone ACKNOWLEDGEMENTS: The authors thank Dr Mark Rollag for the gift of melatonin antiserum R1055. This research was supported by a grant from the National Institutes of Health EY04864. Received 16 September 1998; accepted 7 October 1998 NeuroReport: December 21st, 1998 - Volume 9 - Issue 18 - p 4041-4044 Buy Abstract MELATONIN is synthesized in the chicken retina under the influence of a circadian clock, which also regulates the expression of tryptophan hydroxylase (TPH) and serotonin N-acetyltransferase (AA-NAT). In order to examine the role of substrate supply in the rhythmic synthesis of melatonin in chicken retina, tryptophan and 5-hydroxytryptophan were administered day and night in light or darkness. When administered systemically at night in darkness, 5-hydroxytryptophan, but not tryptophan, dramatically stimulates melatonin levels in the chick retina in a dose-dependent manner. Intraocular administration of 5-hydroxytryptophan also increases melatonin levels locally, indicating a retinal site of action of the serotonin precursor. The effect of 5-hydroxytryptophan is much greater at night, when TPH and AA-NAT activities are high, than during the day, when the enzyme activities are low. Similarly, unexpected light exposure at night, which inactivates AA-NAT, significantly reduces the ability of 5-hydroxytryptophan to increase retinal melatonin levels. The results suggest that TPH, but not AA-NAT or other enzymes in the melatonin biosynthetic pathway, is saturated with substrate in sit u. The rate of melatonin production appears to be a function of the concentration of serotonin, which is regulated by TPH, and by the level of activity of AA-NAT. © 1998 Lippincott Williams & Wilkins, Inc.