Oxytocin down-regulates mesenteric afferent sensitivity via the enteric OTR/nNOS/NO/KATP pathway in rat
1Department of Physiology, Shandong Provincial Key Laboratory of Mental Disorders, Shandong University School of Medicine, Jinan, China.
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.
Key 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 & Inferences:
Oxytocin down-regulates the mesenteric afferent sensitivity through nNOS-NO-KATP pathway. Our findings may reveal a new peripheral mechanism for oxytocin analgesia.
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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