The cyclin-dependent kinase (cdk) inhibitors, olomoucine and roscovitine, alter the expression of a molluscan circadian pacemaker.
1. In this study, we determined the effects of the cyclin-dependent kinase (cdk) inhibitors, olomoucine and roscovitine, on the circadian rhythm of optic nerve impulse activity recorded from the eye of the marine snail Bulla gouldiana. 2. We found that olomoucine lengthened period and altered circadian phase in a dose-dependent manner without appreciably affecting gene transcription or translation. We also found that the more specific cdk inhibitor, roscovitine, was approximately 10-fold more effective in lengthening circadian period, while the inactive analogue, iso-olomoucine, was ineffective. 3. The current results, along with previous results from our laboratory, are consistent with the hypothesis that the biochemical mechanism responsible for generating the ocular circadian rhythm in B. gouldiana is related to the biochemical mechanism that regulates the eukaryotic cell division cycle, i.e., by modulation of the activity of protein kinases belonging to the cdk family.
Krucher
N A
NA
Department of Chemistry, Clarkson University, Potsdam, New York 13699-5805, USA.
Meijer
L
L
Roberts
M H
MH
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003624:Darkness; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007701:Kinetin; D008974:Mollusca / Q000502:physiology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D009799:Ocular Physiological Phenomena / Q000187:drug effects; D017440:Photoperiod; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology*; D000077546:Roscovitine
D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D011687:Purines; D000077546:Roscovitine; D004004:Dichlororibofuranosylbenzimidazole; C090046:olomoucine; D003513:Cycloheximide; D018844:Cyclin-Dependent Kinases; D007701:Kinetin