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

Natsumi Aoki, Hiroyuki Watanabe, Kazuya Okada, Kazuyuki Aoki, Takuma Imanishi, Daisuke Yoshida, Ryosuke Ishikawa, Shigenobu Shibata

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)267-275
Number of pages9
JournalJournal of Pharmacological Sciences
Volume124
Issue number2
DOIs
Publication statusPublished - 2014

Keywords

  • Circadian clock
  • Intestine
  • Serotonin

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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