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

Neurosci Lett. 1997 May 23;227(3):145-8. doi: 10.1016/s0304-3940(97)00312-1.


The mammalian hypothalamic suprachiasmatic nucleus (SCN) is an endogenous pacemaker generating circadian rhythms. SCN activity is synchronized with environmental light/dark cycles by photic information primarily 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 and immunocytochemistry we demonstrate that (1) pituitary adenylate cyclase-activating polypeptide (PACAP) induces the phosphorylation of the transcription factor cAMP response element binding protein (CREB) in the SCN during late subjective day and (2) melatonin inhibits this PACAP-induced phosphorylation. Our data suggest that PACAP is a neurotransmitter which affects gene expression in the SCN probably via the cAMP signaling pathway and that the antagonistic effect of melatonin mirrors a feed-back loop within the circadian system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Rhythm / physiology
  • Cyclic AMP Response Element-Binding Protein / analysis
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Immunoblotting
  • Male
  • Melatonin / metabolism*
  • Neuropeptides / metabolism*
  • Neurotransmitter Agents / metabolism*
  • Phosphorylation
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Rats
  • Rats, Wistar
  • Suprachiasmatic Nucleus / chemistry
  • Suprachiasmatic Nucleus / metabolism*


  • Adcyap1 protein, rat
  • Cyclic AMP Response Element-Binding Protein
  • Neuropeptides
  • Neurotransmitter Agents
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Melatonin