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

TRYPTOPHAN hydroxylase (TPH) is the first enzyme in the biosynthetic pathwa ys of melatonin in photoreceptor cells and of serotonin in amacrine cells. To assess the regulation of TPH activity in photoreceptor cells, we pretrea ted retinas with kainic acid. The neurotoxin selectively killed inner retin al neurons while sparing photoreceptors. TPH activity in both control and k ainate-treated retinas undergoes a day-night rhythm. The rhythms in both pr eparations 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 para llels that of melatonin release. Comparing the mean level of activity in rh ythms of intact and lesioned retinas, we calculate that the TPH activity in photoreceptors represents 24% of the total activity. Therefore, the TPH ac tivity measured in intact retinas reflects mainly the enzymatic activity in serotonergic neurons, masking that from photoreceptors. In contrast, the l evels and diurnal variation of TPH mRNA did not differ in intact and kainat e-lesioned retinas indicating that measurements of TPH mRNA content reflect primarily that in photoreceptor cells. Thus, TPH mRNA levels and enzyme ac tivity are differentially regulated in amacrine neurons and photoreceptor c ells. This differential regulation markedly impacts the patterns of daily r hythms observed in the intact retina. NeuroReport 10:2131-2135. (C) 1999 Li ppincott Williams & Wilkins.