We established an assay system using NIH3T3 cells stably expressing a Bmal1 promoter-driven luciferase reporter gene and used the system to analyze circadian oscillation of the gene. We examined the effects of a Hoasca alkaloid, harmine, which has a wide spectrum of pharmacological actions, on circadian rhythms using the validated assay system. Harmine dose-dependently elongated the circadian period. Furthermore, EMSA and Western blot analysis showed that harmine enhanced the transactivating function of RORα, probably by increasing its nuclear translocation. Exogenous expression of RORα also caused a long period, confirming the phenotype indicated by harmine. These results suggest that harmine extends the circadian period by enhancing RORα function and that harmine is a new candidate that contributes to the control of period length in mammalian cells.
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