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Nociceptin inhibits tonic nitric oxide release in the mouse isolated proximal colon
1School of Biological and Biomedical Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow, UK. j.r.w.menzeis@gcal.ac.uk
Abstract:
Nociceptin/orphanin FQ, the endogenous ligand of the opioid receptor-like (ORL1) receptor, caused contractions in the isolated colon of the mouse. Tetrodotoxin and the nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine also produced contractions which were quantitatively similar to those seen in response to nociceptin. In the presence of either tetrodotoxin or Nomega-nitro-L-arginine, nociceptin was unable to cause a further contraction, whereas the muscarinic receptor agonist carbachol elicited a contractile response. Nociceptin had no contractile activity in colonic preparations contracted by Nomega-nitro-L-arginine then relaxed by addition of the NO donor sodium nitroprusside. These data suggest that nociceptin causes contractions of the mouse proximal colon by inhibiting the tonic, neuronal release of NO.
Insights
Nociceptin/orphanin FQ (N/OFQ) causes mouse colon contractions by inhibiting nitric oxide (NO) release. This peptide, acting on opioid receptor-like (ORL1) receptors, influences gastrointestinal motility via NO pathways.
Area of Science:
- Neuroscience
- Gastroenterology
- Pharmacology
Background:
- Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the opioid receptor-like (ORL1) receptor.
- The role of N/OFQ and nitric oxide (NO) in regulating colonic smooth muscle activity is not fully understood.
Purpose of the Study:
- To investigate the mechanism by which N/OFQ induces contractions in the mouse proximal colon.
- To determine the involvement of NO signaling pathways in N/OFQ-mediated colonic contractions.
Main Methods:
- Isolated mouse proximal colon preparations were used.
- Contractile responses to N/OFQ were measured in the presence and absence of tetrodotoxin (TTX) and Nomega-nitro-L-arginine (L-NNA).
- The effects of NO synthase inhibition and NO donation on N/OFQ activity were examined.
Main Results:
- N/OFQ, tetrodotoxin, and L-NNA all induced similar colonic contractions.
- N/OFQ failed to induce further contractions when NO synthesis was inhibited by TTX or L-NNA.
- Nociceptin did not affect colonic preparations pre-contracted with L-NNA and then relaxed with sodium nitroprusside.
Conclusions:
- Nociceptin/orphanin FQ induces contractions in the mouse proximal colon.
- These contractions are mediated by the inhibition of tonic, neuronal nitric oxide (NO) release.
- N/OFQ's action on ORL1 receptors influences colonic motility through modulation of NO signaling.