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Evoked release of methionine enkephalin from tolerant/dependent enteric ganglia: paradoxical dependence on morphine
Abstract:
Experiments were performed in order to determine whether the state of tolerance to and dependence upon opiates is associated with changes in one or more of the characteristics of the electrically induced release of methionine enkephalin from enteric ganglia. Acute morphine pretreatment substantially reduces the magnitude of the evoked release of this peptide from opiate-naive ilea. However, the rate of the evoked release of enkephalin from morphine-pretreated, tolerant/dependent preparations is indistinguishable from that observed for untreated, naive ilea. Paradoxically, 15 min after acute in vitro withdrawal of morphine form such preparations, the presence of morphine appears to be prerequisite for the manifestation of electrically evoked release of methionine enkephalin. The evoked release of this peptide from ilea 60 min after withdrawal is no longer dependent upon morphine. Moreover, the magnitude of the increase in the rate of enkephalin release from these preparations is almost double that observed for opiate-naive ilea. These data indicate that the manifestation of opiate tolerance/dependence for the release of methionine enkephalin from enteric ganglia comprises several adaptive processes, the consequences of which can be observed at different stages of withdrawal.
Insights
Opiate tolerance and dependence alter methionine enkephalin release from enteric ganglia. Withdrawal reveals complex adaptive processes affecting peptide release at different stages.
Area of Science:
- Neuroscience
- Gastroenterology
- Pharmacology
Background:
- Opiate drugs, like morphine, affect the enteric nervous system.
- Methionine enkephalin is a key peptide neurotransmitter in the gut.
- Understanding opiate effects on gut function is crucial for pain management and addiction research.
Purpose of the Study:
- To investigate how opiate tolerance and dependence change methionine enkephalin release from enteric ganglia.
- To characterize the dynamic alterations in peptide release during morphine withdrawal.
Main Methods:
- Electrically induced release of methionine enkephalin was measured from guinea pig ilea.
- Experiments involved naive, morphine-pretreated (tolerant/dependent), and post-withdrawal preparations.
- Peptide release was assessed at different time points after acute in vitro morphine withdrawal.
Main Results:
- Acute morphine pretreatment reduced evoked methionine enkephalin release in naive ilea.
- In tolerant/dependent ilea, release initially returned to naive levels.
- Paradoxically, release 15 minutes post-withdrawal required morphine, but not at 60 minutes.
- At 60 minutes post-withdrawal, enkephalin release was significantly enhanced compared to naive ilea.
Conclusions:
- Opiate tolerance and dependence involve multiple adaptive processes affecting enteric methionine enkephalin release.
- These adaptive changes manifest dynamically during morphine withdrawal.
- The findings highlight the complex neurochemical adaptations in the gut during chronic opiate exposure and withdrawal.