Involvement of 5-HT<sub>3</sub> and 5-HT<sub>4</sub> Receptors in the Regulation of Circadian Clock Gene Expression in Mouse Small Intestine

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  • Aoki Natsumi
    Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Japan
  • Watanabe Hiroyuki
    Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Japan
  • Okada Kazuya
    Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Japan
  • Aoki Kazuyuki
    Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Japan
  • Imanishi Takuma
    Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Japan
  • Yoshida Daisuke
    Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Japan
  • Ishikawa Ryosuke
    Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Japan
  • Shibata Shigenobu
    Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Japan

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  • Involvement of 5-HT₃ and 5-HT₄ Receptors in the Regulation of Circadian Clock Gene Expression in Mouse Small Intestine

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Abstract

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.

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