Oxytocin regulates gastrointestinal motility, inflammation, macromolecular permeability, and mucosal maintenance in mice

Martha G. Welch, Kara G. Margolis, Zhishan Li, Michael D. Gershon

Research output: Contribution to journalArticlepeer-review


Enteric neurons express oxytocin (OT); moreover, enteric neurons and enterocytes express developmentally regulated OT receptors (OTRs). Although OT (with secretin) opposes intestinal inflammation, physiological roles played by enteric OT/OTR signaling have not previously been determined. We tested hypotheses that OT/OTR signaling contributes to enteric nervous system (ENS)-related gastrointestinal (GI) physiology. GI functions and OT effects were compared in OTR-knockout (OTRKO) and wild-type (WT) mice. Stool mass and water content were greater in OTRKO mice than in WT. GI transit time in OTRKO animals was faster than in WT; OT inhibited in vitro generation of ENS-dependent colonic migrating motor complexes in WT but not in OTRKO mice. Myenteric neurons were hyperplastic in OTRKO animals, and mucosal exposure to cholera toxin (CTX) in vitro activated Fos in more myenteric neurons in OTRKO than WT than in WT mice; OT inhibited the CTX response in WT but not in OTRKO mice. Villi and crypts were shorter in OTRKO than in WT mice, and transit-amplifying cell proliferation in OTRKO crypts was deficient. Macromolecular intestinal permeability in OTRKO was greater than WT mice, and experimental colitis was more severe in OTRKO mice; moreover, OT protected WT animals from colitis. Observations suggest that OT/OTR signaling acts as a brake on intestinal motility, decreases mucosal activation of enteric neurons, and promotes enteric neuronal development and/or survival. It also regulates proliferation of crypt cells and mucosal permeability; moreover OT/OTR signaling is protective against inflammation. Oxytocinergic signaling thus appears to play an important role in multiple GI functions that are subject to neuronal regulation.

Original languageEnglish (US)
Pages (from-to)G848-G862
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number8
StatePublished - Oct 15 2014


  • Colitis
  • Enteric nervous system
  • Nurture
  • Oxytocin receptor knockout

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


Dive into the research topics of 'Oxytocin regulates gastrointestinal motility, inflammation, macromolecular permeability, and mucosal maintenance in mice'. Together they form a unique fingerprint.

Cite this