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 language | English |
---|---|
Pages (from-to) | 267-275 |
Number of pages | 9 |
Journal | Journal of Pharmacological Sciences |
Volume | 124 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2014 |
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Keywords
- Circadian clock
- Intestine
- Serotonin
ASJC Scopus subject areas
- Pharmacology
- Molecular Medicine
Cite this
Involvement of 5-HT3 and 5-HT4 receptors in the regulation of circadian clock gene expression in mouse small intestine. / Aoki, Natsumi; Watanabe, Hiroyuki; Okada, Kazuya; Aoki, Kazuyuki; Imanishi, Takuma; Yoshida, Daisuke; Ishikawa, Ryosuke; Shibata, Shigenobu.
In: Journal of Pharmacological Sciences, Vol. 124, No. 2, 2014, p. 267-275.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Involvement of 5-HT3 and 5-HT4 receptors in the regulation of circadian clock gene expression in mouse small intestine
AU - Aoki, Natsumi
AU - Watanabe, Hiroyuki
AU - Okada, Kazuya
AU - Aoki, Kazuyuki
AU - Imanishi, Takuma
AU - Yoshida, Daisuke
AU - Ishikawa, Ryosuke
AU - Shibata, Shigenobu
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Circadian clock
KW - Intestine
KW - Serotonin
UR - http://www.scopus.com/inward/record.url?scp=84895516084&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84895516084&partnerID=8YFLogxK
U2 - 10.1254/jphs.13253FP
DO - 10.1254/jphs.13253FP
M3 - Article
C2 - 24492464
AN - SCOPUS:84895516084
VL - 124
SP - 267
EP - 275
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
SN - 1347-8613
IS - 2
ER -