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.
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Japan.
Natsumi
N
Aoki
Hiroyuki
H
Watanabe
Kazuya
K
Okada
Kazuyuki
K
Aoki
Takuma
T
Imanishi
Daisuke
D
Yoshida
Ryosuke
R
Ishikawa
Shigenobu
S
Shibata
D056930:ARNTL Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D057906:Circadian Clocks / Q000235:genetics*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000235:genetics*; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D056950:Period Circadian Proteins / Q000235:genetics* / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism / Q000502:physiology*; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism / Q000502:physiology*; D012701:Serotonin / Q000502:physiology; D058827:Serotonin 5-HT3 Receptor Agonists / Q000494:pharmacology; D058828:Serotonin 5-HT4 Receptor Agonists / Q000494:pharmacology
D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D044406:Receptors, Serotonin, 5-HT3; D058827:Serotonin 5-HT3 Receptor Agonists; D058828:Serotonin 5-HT4 Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin