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

Journal of Pharmacological Sciences

Daisuke Yoshida¹  Ryosuke Ishikawa¹  Takuma Imanishi¹  Kazuya Okada¹  Natsumi Aoki¹  Hiroyuki Watanabe¹  Shigenobu Shibata¹  Kazuyuki Aoki¹ 

[1] Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Japan

关键词: circadian clock;    serotonin;    intestine;    5-HT3;    5-HT4;   

DOI  :  10.1254/jphs.13253FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(39)Cited-By(2)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.

【 授权许可】

Unknown