Differential cAMP gating of glutamatergic signaling regulates long-term state changes in the suprachiasmatic circadian clock

J Neurosci. 2000 Oct 15;20(20):7830-7. doi: 10.1523/JNEUROSCI.20-20-07830.2000.

Abstract

We investigated a role for cAMP/protein kinase A (PKA) in light/glutamate (GLU)-stimulated state changes of the mammalian circadian clock in the suprachiasmatic nucleus (SCN). Nocturnal GLU treatment elevated [cAMP]; however, agonists of cAMP/PKA did not mimic the effects of light/GLU. Coincident activation of cAMP/PKA enhanced GLU-stimulated state changes in early night but blocked light/GLU-induced state changes in the late night, whereas inhibition of cAMP/PKA reversed these effects. These responses are distinct from those mediated by mitogen-activated protein kinase (MAPK). MAPK inhibitors attenuated both GLU-induced state changes. Although GLU induced mPer1 mRNA in both early and late night, inhibition of PKA blocked this event only in early night, suggesting that cellular mechanisms regulating mPer1 are gated by the suprachiasmatic circadian clock. These data support a diametric gating role for cAMP/PKA in light/GLU-induced SCN state changes: cAMP/PKA promotes the effects of light/GLU in early night, but opposes them in late night.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Clocks / drug effects
  • Biological Clocks / physiology
  • Cell Cycle Proteins
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / physiology*
  • Cyclic AMP / metabolism*
  • Cyclic AMP / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Darkness
  • Enzyme Inhibitors / pharmacology
  • Glutamic Acid / metabolism*
  • Glutamic Acid / pharmacology
  • Light
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Period Circadian Proteins
  • Photic Stimulation
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Long-Evans
  • Reaction Time / drug effects
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Suprachiasmatic Nucleus / drug effects
  • Suprachiasmatic Nucleus / metabolism*

Substances

  • Cell Cycle Proteins
  • Enzyme Inhibitors
  • Nuclear Proteins
  • Per1 protein, rat
  • Period Circadian Proteins
  • RNA, Messenger
  • Glutamic Acid
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases