Oxytocin down-regulates mesenteric afferent sensitivity via the enteric OTR/nNOS/NO/KATP pathway in rat

J Li1, B Xue, T Han

  • 1Department of Physiology, Shandong Provincial Key Laboratory of Mental Disorders, Shandong University School of Medicine, Jinan, China.

Abstract

Insights

Oxytocin reduces gut sensitivity via a peripheral pathway involving nitric oxide and KATP channels. This finding reveals a novel mechanism for oxytocin

Area of Science:

  • Neuroscience
  • Gastroenterology
  • Pain Research

Background:

  • Oxytocin is known for its pain-modulating effects, primarily studied through central mechanisms.
  • The role of peripheral oxytocin pathways in pain modulation remains largely unexplored.

Purpose of the Study:

  • To investigate the peripheral mechanisms underlying oxytocin's analgesic effects in the gut.
  • To explore the involvement of nitric oxide synthase and its downstream pathways.

Main Methods:

  • Mesenteric afferent discharge was recorded in vitro.
  • Immunofluorescence identified oxytocin receptor (OTR) and neuronal nitric oxide synthase (nNOS) expression.
  • Pharmacological agents including NO donors, NOS inhibitors, and channel blockers were used.

Main Results:

  • Oxytocin attenuated bradykinin- or distention-induced afferent discharge, mimicking nitric oxide (NO) effects.
  • Inhibition of NOS, calcium channels, or KATP channels reduced oxytocin's inhibitory effect.
  • OTR and nNOS were found to be co-localized in the rat jejunum's myenteric plexus.

Conclusions:

  • Oxytocin down-regulates mesenteric afferent sensitivity via the nNOS-NO-KATP pathway.
  • This study identifies a new peripheral mechanism for oxytocin's analgesic action in the gastrointestinal tract.

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