Resetting the biological clock: mediation of nocturnal circadian shifts by glutamate and NO.
Circadian rhythms of mammals are timed by an endogenous clock with a period of about 24 hours located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Light synchronizes this clock to the external environment by daily adjustments in the phase of the circadian oscillation. The mechanism has been thought to involve the release of excitatory amino acids from retinal afferents to the SCN. Brief treatment of rat SCN in vitro with glutamate (Glu), N-methyl-D-aspartate (NMDA), or nitric oxide (NO) generators produced lightlike phase shifts of circadian rhythms. The SCN exhibited calcium-dependent nitric oxide synthase (NOS) activity. Antagonists of NMDA or NOS pathways blocked Glu effects in vitro, and intracerebroventricular injection of a NOS inhibitor in vivo blocked the light-induced resetting of behavioral rhythms. Together, these data indicate that Glu release, NMDA receptor activation, NOS stimulation, and NO production link light activation of the retina to cellular changes within the SCN mediating the phase resetting of the biological clock.
Ding
J M
JM
Department of Cell and Structural Biology, University of Illinois, Urbana 61801.
Chen
D
D
Weber
E T
ET
Faiman
L E
LE
Rea
M A
MA
Gillette
M U
MU
D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D008027:Light; D016202:N-Methylaspartate / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009475:Neurons, Afferent / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012160:Retina / Q000502:physiology; D015398:Signal Transduction; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D018698:Glutamic Acid; D016202:N-Methylaspartate; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester