cGMP-dependent protein kinase inhibitor blocks light-induced phase advances of circadian rhythms in vivo.
The suprachiasmatic nucleus (SCN) contains the primary mammalian circadian clock. Light synchronizes these circadian rhythms through a mechanism involving the release of excitatory amino acids (EAA) and synthesis of nitric oxide (NO) in the SCN. In the current study, we investigated whether cGMP-mediated activation of cGMP-dependent protein kinase (PKG) is associated with light-induced phase shifts of the circadian oscillator. Local administration of the specific PKG inhibitor, KT-5823, significantly attenuated light-induced advances in the phase of activity rhythms when administered during late subjective night (CT 19). Similar treatment at CT 14 had no significant effect on light-induced phase delays. These results are the first to implicate PKG in the biochemical pathway(s) responsible for photic phase advances, and suggest a divergence in biochemical pathways involved in photic phase shifts.
Weber
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ET
Biological Rhythms and Integrative Neuroscience Research Institute, Armstrong Laboratory, Brooks AFB, TX 78235-5104, USA.
Gannon
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Rea
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MA
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles; D002940:Circadian Rhythm / Q000187:drug effects* / Q000528:radiation effects*; D006224:Cricetinae; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D007211:Indoles; D007276:Injections, Intraventricular; D008027:Light; D008647:Mesocricetus; D013493:Suprachiasmatic Nucleus / Q000502:physiology
D000470:Alkaloids; D002227:Carbazoles; D007211:Indoles; C073601:KT 5823; D017869:Cyclic GMP-Dependent Protein Kinases