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In vivo modulation of small bowel motility by morphine and D-Ala2 D-Leu5 enkephalin
Abstract:
The effects of morphine and D-Ala2 D-Leu5 enkephalin (DADLE) on intestinal motility were studied in conscious dogs with chronically implanted electrodes. In fed dogs, the normal pattern of irregular spike activity was interrupted by morphine and DADLE; both induced regular spike activity whilst DADLE also induced quiescence. Mr2266 and naloxone abolished the regular spike activity response to morphine and DADLE, but not the quiescence induced by DADLE. Mr2267 had no antagonistic action. Nalorphine methiodide induced a morphine-like response; lower doses had no agonistic action but abolished the response to morphine. The results suggest that regular spike activity induced by morphine and DADLE is a mu receptor effect, whilst the quiescence induced by DADLE may be a delta receptor effect. Morphine appears to have a peripheral site of action.
Insights
Morphine and D-Ala2 D-Leu5 enkephalin (DADLE) affect intestinal motility in dogs. Regular spike activity is a mu receptor effect, while DADLE-induced quiescence may involve delta receptors, suggesting peripheral action for morphine.
Area of Science:
- Gastroenterology
- Pharmacology
- Neuroscience
Background:
- Opioid receptors play a crucial role in regulating gastrointestinal motility.
- Understanding the specific receptor interactions of different opioids is essential for therapeutic applications.
Purpose of the Study:
- To investigate the effects of morphine and D-Ala2 D-Leu5 enkephalin (DADLE) on canine intestinal motility.
- To differentiate the receptor mechanisms underlying opioid-induced changes in intestinal activity.
Main Methods:
- Utilized chronic electrode implantation in conscious dogs to monitor intestinal electrical activity.
- Administered morphine and DADLE, followed by assessments with opioid antagonists Mr2266, naloxone, and nalorphine methiodide.
Main Results:
- Both morphine and DADLE induced regular spike activity, disrupting normal motility patterns.
- DADLE also induced a quiescent state, which was not antagonized by naloxone.
- Opioid antagonists Mr2266 and naloxone blocked the regular spike activity response to both drugs.
Conclusions:
- Regular spike activity induced by morphine and DADLE is mediated by mu-opioid receptors.
- DADLE-induced quiescence may be mediated by delta-opioid receptors, indicating distinct receptor pathways.
- Morphine's effects on intestinal motility appear to involve peripheral receptor sites.