THE PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE-INDUCED PHOSPHORYLATION OF THE TRANSCRIPTION FACTOR CREB (CAMP RESPONSE ELEMENT-BINDING PROTEIN) IN THE RAT SUPRACHIASMATIC NUCLEUS IS INHIBITED BY MELATONIN

The mammalian hypothalamic suprachiasmatic nucleus (SCN) is an endogen ous pacemaker generating circadian rhythms. SCN activity is synchroniz ed with environmental light/dark cycles by photic information primaril y transmitted via the retinohypothalamic tract (RHT). The SCN controls synthesis and release of melatonin, the hormone of the pineal gland. Melatonin itself feeds back to the SCN. Using brain slice technique an d immunocytochemistry we demonstrate that (1) pituitary adenylate cycl ase-activating polypeptide (PACAP) induces the phosphorylation of the transcription factor cAMP response element binding protein (CREB) in t he SCN during late subjective day and (2) melatonin inhibits this PACA P-induced phosphorylation. Our data suggest that PACAP is a neurotrans mitter which affects gene expression in the SCN probably via the cAMP signaling pathway and that the antagonistic effect of melatonin mirror s a feed-back loop within the circadian system. (C) 1997 Elsevier Scie nce Ireland Ltd.