gamma-endorphin--des-tyr(1)- and Opioid-Related-Disorders

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.

Topics: Analgesics, Opioid; Animals; Antidepressive Agents; beta-Endorphin; Dose-Response Relationship, Drug; Endorphins; Guinea Pigs; Ileum; Male; Morphine; Muscle Contraction; Opioid-Related Disorders; Peptide Fragments; Substance Withdrawal Syndrome