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 regulation of tryptophan hydroxylase activity localized in retinal photoreceptor cells of Xenopus laevis, where the enzyme plays a key role in circadian melatonin biosynthesis. In photoreceptor-enriched retinas that lack serotonergic neurons, tryptophan hydroxylase activity is markedly stimulated by treatments that increase intracellular levels of cyclic AMP or activate cyclic AMP-dependent protein kinase, including forskolin, phosphodiesterase inhibitors, and cyclic AMP analogues. In contrast, cyclic AMP has no effect on tryptophan hydroxylase mRNA abundance. Experiments using cycloheximide and actinomycin D demonstrate that cyclic AMP exerts its regulatory effect via posttranslational 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 stimulatory effect of forskolin and that of darkness are inhibited by H89, an inhibitor of cyclic AMP-dependent protein kinase. In conclusion, cyclic AMP may mediate the acute effects of light and darkness on tryptophan hydroxylase activity of retinal photoreceptor cells.
Valenciano
A I
AI
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322-3090, USA.
Alonso-Gómez
A L
AL
Iuvone
P M
PM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D008027:Light; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D020419:Photoreceptor Cells, Vertebrate / Q000201:enzymology* / Q000528:radiation effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000528:radiation effects; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism*
D019384:Nucleic Acid Synthesis Inhibitors; D010726:Phosphodiesterase Inhibitors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D005576:Colforsin; D003513:Cycloheximide; D000242:Cyclic AMP; D014365:Tryptophan Hydroxylase; D015056:1-Methyl-3-isobutylxanthine