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Peripheral effects of naloxone in mice with acute diarrhea associated with intestinal inflammation
1Department of Anaesthesiology, Hospital Universitario del Mar, Barcelona, Spain.
Abstract:
The aim of the study was to evaluate the effects of centrally and peripherally acting opioid antagonists such as naloxone (NX), naloxone methiodide, (+)-naloxone [(+)NX], (-)-a-5,9-diethyl-2'-hydroxy-2 (3-furylmethyl)-6,7-benzomorphan and naltrindole on gastrointestinal (GI) transit in mice with diarrhea associated with intestinal inflammation. Our hypothesis was that diarrhea/inflammation could induce a release of endogenous opioid peptides that would play an inhibitory role in the physiological response to intestinal inflammation; the administration of opioid antagonists would uncover the effects of the endogenous opioid peptides on the gut. Diarrhea associated with inflammation was induced in mice by administration of croton oil (CO) although control animals received saline (SS); GI transit was evaluated with a charcoal meal. The i.p. administration of 0.1 mg/kg NX or NXME, induced a significant increase in GI transit in CO but not in SS-treated animals (P < .005). At the same dose, (+)NX had no effect either in CO or SS groups. The kappa antagonist MR-2266 (1 and 3 mg/kg) had no effect on GI transit in SS or CO animals. However, the delta antagonist naltrindole (3 mg/kg), caused a small but significant (P < .01) increase in GI transit in the CO group. These results suggest that endogenous opioid peptides are released in CO-treated animals and exert an inhibitory control of intestinal motility, which is unmasked by opioid antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Opioid antagonists like naloxone significantly increased gastrointestinal transit in mice with inflammatory diarrhea, suggesting endogenous opioids normally slow the gut during inflammation. This unmasks their inhibitory role.
Area of Science:
- Pharmacology
- Gastroenterology
- Neuroscience
Background:
- Inflammation-induced diarrhea involves complex physiological responses.
- Endogenous opioid peptides may play a role in regulating gastrointestinal motility during inflammation.
Purpose of the Study:
- To investigate the effects of opioid antagonists on gastrointestinal transit in mice with experimentally induced diarrhea and inflammation.
- To test the hypothesis that endogenous opioid peptides inhibit gut motility during inflammation.
Main Methods:
- Diarrhea and inflammation were induced using croton oil (CO) in mice.
- Gastrointestinal transit was measured using a charcoal meal after administration of various opioid antagonists (naloxone, naltrindole, etc.).
Main Results:
- Naloxone and naloxone methiodide significantly increased gastrointestinal transit in CO-treated mice but not controls.
- The delta-opioid antagonist naltrindole also significantly increased transit in CO-treated mice.
- (+)-naloxone and the kappa-opioid antagonist MR-2266 showed no significant effects.
Conclusions:
- Endogenous opioid peptides are released during intestinal inflammation and exert an inhibitory effect on gut motility.
- Opioid antagonists can unmask this endogenous opioid-mediated inhibition of intestinal transit.