Neuroreport 1999 Jul 13;1010:2131-5. doi: 10.1097/00001756-199907130-00025.

Diurnal rhythms of tryptophan hydroxylase activity in Xenopus laevis retina: opposing phases in photoreceptors and inner retinal neurons.

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Tryptophan hydroxylase (TPH) is the first enzyme in the biosynthetic pathways of melatonin in photoreceptor cells and of serotonin in amacrine cells. To assess the regulation of TPH activity in photoreceptor cells, we pretreated retinas with kainic acid. The neurotoxin selectively killed inner retinal neurons while sparing photoreceptors. TPH activity in both control and kainate-treated retinas undergoes a day-night rhythm. The rhythms in both preparations fit sinusoidal functions. However, the rhythm in intact retinas peaks at midday while that in kainate-lesioned retinas does so at midnight. The daily rhythm of tryptophan hydroxylase activity in photoreceptors parallels that of melatonin release. Comparing the mean level of activity in rhythms of intact and lesioned retinas, we calculate that the TPH activity in photoreceptors represents 24% of the total activity. Therefore, the TPH activity measured in intact retinas reflects mainly the enzymatic activity in serotonergic neurons, masking that from photoreceptors. In contrast, the levels and diurnal variation of TPH mRNA did not differ in intact and kainate-lesioned retinas indicating that measurements of TPH mRNA content reflect primarily that in photoreceptor cells. Thus, TPH mRNA levels and enzyme activity are differentially regulated in amacrine neurons and photoreceptor cells. This differential regulation markedly impacts the patterns of daily rhythms observed in the intact retina.

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