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Gastric cytoprotective effect of morphine is probably not mediated by mu-receptors
S A Bhounsule1, R S D'Souza, V G Dhume
1Department of Pharmacology, Goa Medical College, India.
Abstract:
Morphine has a significant protective effect on ethanol-induced gastric lesions. This effect is antagonized by naloxone, suggesting that it is mediated by opioid receptors. In the rat, mu-receptors have been shown to be involved in other gastrointestinal actions of opioids. However, the potent partial agonist at mu-receptors, buprenorphine, not only failed to protect but actually aggravated ethanol-induced lesions at higher doses. The gut-selective mu-agonist, loperamide, also did not have a protective effect, while the mixed opioid, pentazocine, which has an antagonistic action at mu-receptors, by itself protected against ethanol-induced gastric lesions. Our results suggest that mu-receptors are probably not involved in the gastric cytoprotective action of opioids.
Insights
Morphine protects against ethanol-induced gastric lesions, but this effect is not mediated by mu-opioid receptors. Other opioids targeting these receptors failed to show protection, suggesting a different mechanism for opioid-induced gastric cytoprotection.
Area of Science:
- Pharmacology
- Gastroenterology
- Toxicology
Background:
- Opioids are known to affect gastrointestinal functions.
- Morphine demonstrates a protective effect against ethanol-induced gastric lesions.
- This protective effect is antagonized by naloxone, indicating involvement of opioid receptors.
Purpose of the Study:
- To investigate the role of mu-opioid receptors in the gastric cytoprotective effects of opioids against ethanol-induced lesions.
- To determine if specific mu-receptor agonists or antagonists influence the protective action of morphine.
Main Methods:
- Administration of morphine, buprenorphine (a mu-partial agonist), loperamide (a gut-selective mu-agonist), and pentazocine (a mixed opioid with mu-antagonism) to rats.
- Induction of gastric lesions using ethanol.
- Assessment of the protective or aggravating effects of the tested opioids on gastric lesions.
Main Results:
- Morphine exhibited significant protection against ethanol-induced gastric lesions.
- Buprenorphine aggravated lesions at higher doses, and loperamide showed no protective effect.
- Pentazocine, a mu-receptor antagonist, demonstrated protective effects on its own.
- Naloxone, an opioid antagonist, reversed the protective effect of morphine.
Conclusions:
- The findings suggest that mu-opioid receptors are not involved in the gastric cytoprotective action of opioids against ethanol-induced damage.
- The mechanism underlying opioid-induced gastric protection likely involves other receptor systems.
- Further research is needed to elucidate the specific pathways mediating opioid-induced gastroprotection.