Regulation of tryptophan hydroxylase activity in Xenopus laevis photoreceptor cells by cyclic AMP

The aim of this study was to investigate the role of cyclic AMP in the regu lation of tryptophan hydroxylase activity localized in retinal photorecepto r cells of Xenopus laevis, where the enzyme plays a key role in circadian m elatonin biosynthesis. In photoreceptor-enriched retinas that lack serotone rgic neurons, tryptophan hydroxylase activity is markedly stimulated by tre atments that increase intracellular levels of cyclic AMP or activate cyclic AMP-dependent protein kinase, including forskolin, phosphodiesterase inhib itors, and cyclic AMP analogues. In contrast, cyclic AMP has no effect on t ryptophan hydroxylase mRNA abundance. Experiments using cycloheximide and a ctinomycin D demonstrate that cyclic AMP exerts its regulatory effect via p osttranslational mechanisms mediated by cyclic AMP-dependent protein kinase . The effect of cyclic AMP is independent of the phase of the photoperiod, suggesting that the nucleotide is not a mediator of the circadian rhythm of tryptophan hydroxylase. Cyclic AMP accumulation is higher in darkness than in light, as is tryptophan hydroxylase activity. Furthermore, the stimulat ory effect of forskolin and that of darkness are inhibited by H89, an inhib itor of cyclic AMP-dependent protein kinase. In conclusion, cyclic AMP may mediate the acute effects of light and darkness on tryptophan hydroxylase a ctivity of retinal photoreceptor cells.