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Beta-endorphin fragments (DT gamma E and DE gamma E) reduce opiate withdrawal in guinea pig ileum
1Dipartimento di Scienze Farmaceutiche, Università di Salerno, Italy. annacap@unisa.it
Abstract:
The effect exerted by two beta-endorphin fragments (DTgammaE and DEgammaE) was investigated on the acute opioid dependence induced by mu, kappa and delta receptor agonists in vitro. After a 4-min in vitro exposure to morphine (less selective mu agonist), DAGO (highly selective mu agonist), U50-488H (highly selective kappa agonist) and beta-endorphin (selective mu-delta agonist), a strong contracture of guinea pig isolated ileum was observed after the addition of naloxone. This effect was also observed when rabbit isolated jejunum was pretreated with deltorphin (highly selective delta agonist). DTgammaE or DEgammaE injection treatment before or after morphine, DAGO, U50-488H, beta-endorphin or deltorphin were able to both prevent and reverse the naloxone-induced contracture after exposure to the opioid agonists in a concentration-dependent fashion. Our results indicate that both DTgammaE or DEgammaE are able to reduce significantly opioid dependence in vitro, suggesting an important functional interaction between beta-endorphin fragments and opioid dependence induced by mu, kappa and delta receptors.
Insights
Two beta-endorphin fragments, DTgammaE and DEgammaE, significantly reduced acute opioid dependence in vitro. These fragments prevented and reversed naloxone-induced contractures, suggesting a key interaction with opioid receptors.
Area of Science:
- Pharmacology
- Neuroscience
- Molecular Biology
Background:
- Opioid dependence is a significant health issue.
- Opioid receptors (mu, kappa, delta) mediate various physiological effects.
- Beta-endorphins are endogenous peptides with opioid-like activity.
Purpose of the Study:
- To investigate the effect of beta-endorphin fragments (DTgammaE and DEgammaE) on acute opioid dependence in vitro.
- To determine if these fragments can prevent or reverse opioid-induced dependence.
Main Methods:
- In vitro experiments using guinea pig isolated ileum and rabbit isolated jejunum.
- Exposure to mu, kappa, and delta receptor agonists (morphine, DAGO, U50-488H, beta-endorphin, deltorphin).
- Assessment of naloxone-induced contracture following agonist exposure and treatment with DTgammaE or DEgammaE.
Main Results:
- Opioid agonists induced significant naloxone-precipitated contractures in isolated tissues.
- DTgammaE and DEgammaE treatments prevented and reversed these contractures in a concentration-dependent manner.
- Both fragments demonstrated significant reduction of opioid dependence in vitro.
Conclusions:
- DTgammaE and DEgammaE effectively reduce acute opioid dependence induced by mu, kappa, and delta receptor agonists.
- These findings suggest a significant functional interaction between beta-endorphin fragments and opioid receptor systems.
- Beta-endorphin fragments may represent a novel therapeutic target for managing opioid dependence.