Analyses of signal transduction cascades reveal an essential role of calcium ions for regulation of melatonin biosynthesis in the light-sensitive pineal organ of the rainbow trout (Oncorhynchus mykiss).
Signal transduction processes regulating melatonin production in the light-sensitive trout pineal organ were investigated by immunocytochemical and immunochemical demonstration of phosphorylated cyclic AMP-responsive element-binding protein (pCREB) and measurements of cyclic AMP, melatonin, and calcium levels. Melatonin levels were tightly controlled by light and darkness. Elevation of cyclic AMP levels by 8-bromo-cyclic AMP, forskolin, and 3-isobutyl-1-methylxanthine increased the levels of pCREB and melatonin in light- or dark-adapted pineal organs in vitro. Without pharmacological treatment, the levels of pCREB and cyclic AMP remained constant for several hours before and after light onset. Inhibition of cyclic AMP-dependent proteasomal proteolysis by lactacystin, MG 132, and calpain inhibitor I did not prevent the rapid, light-induced suppression of melatonin biosynthesis. However, changes in the intracellular calcium concentration by drugs affecting voltage-gated calcium channels of the L type and intracellular calcium oscillations (cobalt chloride, nifedipine, Bay K 8644) had dramatic effects on the rapid, light-dependent changes in melatonin levels. These effects were not accompanied by changes in cyclic AMP levels. Thus, the rapid, light-dependent changes in melatonin levels in the trout pineal organ are regulated apparently by a novel calcium signaling pathway and do not involve changes in cyclic AMP levels, cyclic AMP-dependent proteasomal proteolysis, or phosphorylation of cyclic AMP-responsive element-binding protein.
Kroeber
S
S
Dr. Senckenbergische Anatomie, Department of Anatomy II, Johann Wolfgang Goethe University Frankfurt, Germany.
Meissl
H
H
Maronde
E
E
Korf
H W
HW
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000032:analysis / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D008550:Melatonin / Q000235:genetics*; D009097:Multienzyme Complexes / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000502:physiology*; D009924:Organ Culture Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D010775:Photic Stimulation; D010870:Pineal Gland / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein; D009097:Multienzyme Complexes; D010726:Phosphodiesterase Inhibitors; D005576:Colforsin; D000242:Cyclic AMP; D001191:Arylamine N-Acetyltransferase; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008550:Melatonin; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine