title: Oxytocin down-regulates mesenteric afferent sensitivity via the enteric OTR/nNOS/NO/KATP pathway in rat.
abstract: BACKGROUND
  Oxytocin plays an analgesic role in modulation of nociception and pain. Most work to date has focused on the central mechanisms of oxytocin analgesia, but little is known about whether peripheral mechanisms are also involved.
  
  
  METHODS
  The mesenteric afferent discharge was recorded in vitro. The expressions of oxytocin receptor (OTR) and neuronal nitric oxide synthase (nNOS) in longitudinal muscle myenteric plexus (LMMP) was identified by immunofluorescence.
  
  
  RESULTS
  Oxytocin per se had no effect on the jejunal mesenteric afferent discharge, however, it markedly attenuated the bradykinin- or distention-evoked increase of mesenteric afferent discharge, which was mimiced by the nitric oxide (NO) donor sodium nitroprusside (SNP). Pretreatment of either NOS inhibitor L-NAME or NPLA largely reduced the inhibitory effect of oxytocin on bradykinin-evoked mesenteric afferent discharge. Such effect, to a large extent, was also alleviated by N-and P-type voltage-dependent calcium channel antagonists or KATP blocker glibenclamide. In addition, immunofluorescence studies show strong colocalization of OTR with nNOS in LMMP of the rat jejunum.
  
  
  CONCLUSIONS
  Oxytocin down-regulates the mesenteric afferent sensitivity through nNOS-NO-KATP pathway. Our findings may reveal a new peripheral mechanism for oxytocin analgesia.
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Mental Disorders, Shandong University School of Medicine, Jinan, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: B
authors.initials: B
authors.lastname: Xue
authors.forename: T
authors.initials: T
authors.lastname: Han
authors.forename: K
authors.initials: K
authors.lastname: Huang
authors.forename: L
authors.initials: L
authors.lastname: Gong
authors.forename: X
authors.initials: X
authors.lastname: Ma
authors.forename: K
authors.initials: K
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Cui
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Kunze
authors.forename: C
authors.initials: C
authors.lastname: Liu
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D007583:Jejunum / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D054086:KATP Channels / Q000378:metabolism; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010121:Oxytocin / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D054086:KATP Channels; D018045:Receptors, Oxytocin; C588222:oxytocin receptor, rat; D009569:Nitric Oxide; D010121:Oxytocin; D052248:Nitric Oxide Synthase Type I; D001920:Bradykinin
keywords: mesenteric afferent nerves; nitric oxide; nociception; oxytocin; visceral hyperalgeisa