Involvement of 5-HT3 and 5-HT4 receptors in the regulation of circadian clock gene expression in mouse small intestine

Several lines of evidence suggest that 5-ht receptors play a critical role in the expression of clock genes in the suprachiasmatic nucleus,the main circadian oscillator in hamsters. the contributions of 5-ht-receptor subtypes in the intestine,where they are expressed at high concentrations,are however not yet clarified. the 5-ht synthesis inhibitor,p-chlorophenylalanine,attenuated the daily rhythm of per1 and per2 gene expression in the intestine. injection of 5-ht and agonists of the 5-ht3 and 5-ht4 receptors increased per1/per2 expression and decreased bmal1 expression in a dose-dependent manner. although treatment with antagonists of 5-ht3 and 5-ht4 alone did not affect clock gene expression,co-injection of these antagonists with 5-ht blocked the 5-ht-induced changes in clock gene expression. increased tissue levels of 5-ht due to treatment with the antidepressants clomipramine and fluvoxamine did not affect clock gene expression. the present results suggest that the 5-ht system in the small intestine may play a critical role in regulating circadian rhythms through 5-ht3/5-ht4-receptor activation. © 2014 the japanese pharmacological society.