Rhythmicity of the cGMP-related signal transduction pathway in the mammalian circadian system

Entrainment of mammalian circadian rhythms requires the activation of speci fic signal transduction pathways in the suprachiasmatic nuclei (SCN). Pharm acological inhibition of kinases such as cGMP-dependent kinase (PKG) or Ca2 +/calmodulin-dependent kinase, but not cAMP-dependent kinase, blocks the ci rcadian responses to light in vivo. Here we show a diurnal and circadian rh ythm of cGMP levels and PKG activity in the hamster SCN, with maximal value s during the day or subjective day. This rhythm depends on phosphodiesteras e but not on guanylyl cyclase activity. Five-minute light pulses increased cGMP levels at the end of the subjective night [circadian time 18 (CT18)], but not at CT13.5. Western blot analysis indicated that the PKG II isoform is the one present in the SCN. Inhibition of PKG or guanylyl cyclase in viv o significantly attenuated light-induced phase shifts at CT18 (after 5-min light pulses) but did not affect c-Fos expression in the SCN. These results suggest that cGMP and PKG are related to SCN responses to light and underg o diurnal and circadian changes.