Abstract
In the mouse, activity phase-shifts of the endogenous clock in the suprachiasmatic nucleus (SCN) are associated with phosphorylation of the transcription factor Ca2+/cAMP responsive element binding protein (CREB). CREB phosphorylation is induced by the retino-hypothalamic transmitter pituitary adenylate cyclase-activating polypeptide (PACAP). As detected by immunohistochemistry in SCN slices from wild-type mice, melatonin completely blocked PACAP-stimulated CREB phosphorylation at low concentrations (1 nM). In Mel1a melatonin receptor-deficient mice, the PACAP-induced CREB phosphorylation was inhibited only at melatonin concentrations of 100 nM. This inhibition was, however, blunted by blocking the Mel1b melatonin receptor. Thus, melatonin modulates PACAP-mediated retinal stimuli for clock entrainment primarily via the Mel1a melatonin receptor through molecular interaction within the cAMP-signalling pathway.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cyclic AMP Response Element-Binding Protein / antagonists & inhibitors
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Cyclic AMP Response Element-Binding Protein / physiology*
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In Vitro Techniques
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Male
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Melatonin / pharmacology
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Melatonin / physiology*
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Mice
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Mice, Mutant Strains / genetics
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Neuropeptides / pharmacology
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Neurotransmitter Agents / pharmacology
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Osmolar Concentration
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Phosphorylation / drug effects
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Cell Surface / antagonists & inhibitors
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Receptors, Cell Surface / physiology*
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Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
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Receptors, Cytoplasmic and Nuclear / physiology*
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Receptors, Melatonin
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Reference Values
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Suprachiasmatic Nucleus / drug effects
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Suprachiasmatic Nucleus / physiology*
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Transcription, Genetic / physiology*
Substances
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Adcyap1 protein, mouse
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Cyclic AMP Response Element-Binding Protein
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Neuropeptides
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Neurotransmitter Agents
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Cell Surface
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Receptors, Cytoplasmic and Nuclear
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Receptors, Melatonin
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Melatonin