Dynorphin-(1-13) restores the potency of morphine on the tolerant guinea pig ileum.
Since it has been reported that dynorphin (1-13) enhances the analgetic effects of morphine in mice tolerant either to morphine or beta-endorphin and modulates opioid agonist binding in the tolerant state, experiments were initiated to determine whether comparable phenomenon could be obtained in vitro with dynorphin-(1-13) on the isolated longitudinal muscle of the guinea pig ileum. In the guinea pig ileum rendered tolerant to morphine dynorphin-(1-13) was found to cause a dose-dependent restoration in sensitivity to the inhibitory action of morphine. This phenomenon appeared specific for dynorphin-(1-13) since [Leu5]enkephalin, beta-endorphin, and ethylketocyclazocine did not change significantly the IC50 of morphine in the tolerant preparation. Furthermore, dynorphin-(1-13) attenuated the contraction elicited by naloxone in the morphine tolerant-dependent tissue. It is concluded, that dynorphin-(1-13) restores sensitivity to morphine in the tolerant-dependent state by a modulatory effect probably on the mu receptor that is distinct from its kappa action.
D000818:Animals; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D004361:Drug Tolerance; D004399:Dynorphins / Q000494:pharmacology*; D004723:Endorphins / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000494:pharmacology; D016314:Ethylketocyclazocine; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D001615:beta-Endorphin
D004723:Endorphins; D010446:Peptide Fragments; D009270:Naloxone; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; D001615:beta-Endorphin; C026843:dynorphin (1-13); D004399:Dynorphins; D009020:Morphine; D003496:Cyclazocine