Central 5-hydroxytryptamine (5-HT) mediates colonic motility by hypothalamus oxytocin-colonic oxytocin receptor pathway

Tao Fang Xi, Dan Ni Li, Yu Yian Li, Ying Qin, Hai Hong Wang, Ning Ning Song, Qiong Zhang, Yu Qiang Ding, Xuan Zheng Shi, Dong Ping Xie

Research output: Contribution to journalArticle

Abstract

Gut-derived 5-hydroxytryptamine (5-HT) is well known for its role in mediating colonic motility function. However, it is not very clear whether brain-derived 5-HT is involved in the regulation of colonic motility. In this study, we used central 5-HT knockout (KO) mice to investigate whether brain-derived 5-HT mediates colonic motility, and if so, whether it involves oxytocin (OT) production in the hypothalamus and OT receptor in the colon. Colon transit time was prolonged in KO mice. The OT levels in the hypothalamus and serum were decreased significantly in the KO mice compared to wild-type (WT) controls. OT increased colonic smooth muscle contraction in both KO and WT mice, and the effects were blocked by OT receptor antagonist and tetrodotoxin but not by hexamethonium or atropine. Importantly, the OT-induced colonic smooth muscle contraction was decreased significantly in the KO mice relative to WT. The OT receptor expression of colon was detected in colonic myenteric plexus of mice. Central 5-HT is involved in the modulation of colonic motility which may modulate through its regulation of OT synthesis in the hypothalamus. Our results reveal a central 5-HT - hypothalamus OT - colonic OT receptor axis, providing a new target for the treatment of brain-gut dysfunction.

Original languageEnglish (US)
Pages (from-to)959-964
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume508
Issue number3
DOIs
StatePublished - Jan 15 2019

Keywords

  • Central 5-HT
  • Colonic motility
  • Oxytocin
  • Oxytocin receptor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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