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Effects of mu-opioid receptor agonists on intestinal secretion and permeability during acute intestinal inflammation
1Anesthesiology Research Unit, Institut Municipal Investigació Mèdica, Department of Anesthesiology, Hospital Universitario del Mar, C/ Dr Aiguader, 80, 08003, Barcelona, Spain.
Abstract:
We evaluated and compared the effects of mu-opioid receptor agonists on mucosal fluid transport and permeability, during acute intestinal inflammation. We hypothesized that inflammation would sensitize mu-opioid receptors in the submucosal plexus and/or enterocytes enhancing the effects of mu-opioid receptor agonists. Inflammation was induced by intragastric administration of croton oil, whereas controls received saline. Fluid transport was assessed by enteropooling, and intestinal permeability by blood-to-lumen passage of [51Cr] etylenediaminetetraacetate ([51Cr] EDTA). Intestinal inflammation induced a significant increase in enteropooling (1.9 times) and permeability (2.5 times). In saline- and croton oil-treated animals, mu-opioid receptor agonists produced dose-related inhibitions of enteropooling and intestinal permeability. During inflammation, the potency of morphine increased 4.8 and 3.7 times, inhibiting enteropooling and intestinal permeability, respectively; the potencies of fentanyl and PL017 similarly increased by approximately three (enteropooling) and two times (permeability) in croton oil animals. All effects were reversed by naloxone and naloxone methiodide. The results show that inflammation increases the inhibitory potency of mu-opioid receptor agonists on secretion and permeability, suggesting a sensitization of peripheral mu-opioid receptors.
Insights
Intestinal inflammation enhances the effects of mu-opioid receptor agonists on fluid secretion and permeability. This suggests peripheral mu-opioid receptors become more sensitive during inflammation, impacting gut function.
Area of Science:
- Gastroenterology
- Pharmacology
- Neuroscience
Background:
- Mu-opioid receptor agonists influence intestinal mucosal fluid transport and permeability.
- The impact of acute intestinal inflammation on these effects is not fully understood.
- Inflammation may sensitize peripheral mu-opioid receptors.
Purpose of the Study:
- To evaluate and compare the effects of mu-opioid receptor agonists on mucosal fluid transport and permeability during acute intestinal inflammation.
- To test the hypothesis that inflammation sensitizes peripheral mu-opioid receptors.
Main Methods:
- Acute intestinal inflammation was induced using croton oil in animal models.
- Fluid transport was measured by enteropooling.
- Intestinal permeability was assessed using [51Cr] ethylenediaminetetraacetate ([51Cr] EDTA) blood-to-lumen passage.
- The effects of mu-opioid receptor agonists (morphine, fentanyl, PL017) and their reversal by naloxone were evaluated.
Main Results:
- Intestinal inflammation significantly increased enteropooling (1.9-fold) and permeability (2.5-fold).
- Mu-opioid receptor agonists dose-dependently inhibited enteropooling and permeability in both control and inflamed states.
- During inflammation, the potency of morphine, fentanyl, and PL017 increased significantly for inhibiting enteropooling and permeability.
- These enhanced effects were reversed by naloxone and naloxone methiodide.
Conclusions:
- Acute intestinal inflammation enhances the inhibitory potency of mu-opioid receptor agonists on intestinal secretion and permeability.
- Results suggest a sensitization of peripheral mu-opioid receptors in the submucosal plexus and/or enterocytes during inflammation.
- This sensitization may represent a key mechanism modulating gut function during inflammatory conditions.