Melatonin limits transcriptional impact of phosphoCREB in the mouse SCN via the Mel(1a) receptor

In the mouse, activity phase-shifts of the endogenous clock in the suprachi asmatic nucleus (SCN) are associated with phosphorylation of the transcript ion factor Ca2+/cAMP responsive element binding protein (CREB). CREB phosph orylation is induced by the retino-hypothalamic transmitter pituitary adeny late cyclase-activating polypeptide (PACAP). As detected by immunohistochem istry in SCN slices from wild-type mice, melatonin completely blocked PACAP -stimulated CREB phosphorylation at low concentrations (I nM). In Mel(la) m elatonin receptor-deficient mice, the PACAP-induced CREB phosphorylation wa s inhibited only at melatonin concentrations of 100 nM. This inhibition was , however, blunted by blocking the Mel(lb) melatonin receptor. Thus, melato nin modulates PACAP-mediated retinal stimuli for clock entrainment primaril y via the Melt, melatonin receptor through molecular interaction within the cAMP-signalling pathway. NeuroReport 11:1803-1807 (C) 2000 Lippincott Will iams & Wilkins.