Cgmp-dependent protein kinase inhibitors block light-induced phase
advances of circadian rhythms in vivo.
Mathur, Anuradha, Diego A. Golombek, and Martin R. Ralph.
Department of Psychology, University of Toronto, Toronto, Ontario
M5S 1A1, CANADA
APStracts 2:0337R, 1995.
Synchronization of circadian rhythms is thought to be accomplished
primarily through daily phase delays and advances of the endogenous
circadian clock which in ma als is located in the hypothalamic
suprachiasmatic nucleus (SCN). In the SCN, numerous second messenger
pathways may participate in photic signal transduction. In these
studies, the involvement of cyclic nucleotide-dependent kinases was
examined in vivo using inhibitors of cAMP-dependent kinase (PKA) and
cGMP-dependent kinase (PKG). In constant dark, selective and non
-selective inhibitors of PKG injected near the SCN of hamsters, had no
effect on phase delays produced by light pulses given in the early
subjective night (early in the animals' active period), but
significantly attenuated phase advances induced late in the
subjective night. PKA inhibition had no effect at either time point.
In addition, cGMP agonists had no effect on rhythmicity in the
absence of light. The results suggest that PKG activity is necessary
but not sufficient for normal photic responsiveness and that PKA
activity is not required. The phase dependence of the effect of PKG
inhibition supports the notion that photic entrainment is influenced
by biochemical pathways that differentially regulate sensitivity in a
phase-dependent manner.
Received 27 February 1995; accepted in final form 1 November
1995.
APS Manuscript Number R137-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95