title: Improved assays for the assessment of kappa- and delta-properties of opioid ligands.
abstract: The highly selective non-equilibrium mu-antagonist beta-funaltrexamine (beta-FNA) produced a maximal 20-fold shift in the IC50 for the mu-agonist morphine on the guinea-pig ileum preparation, whilst producing no significant change in the IC50 for the kappa-agonist ethylketazocine. On preparations pretreated with beta-FNA, the pA2 values for the interaction of morphine and ethylketazocine with naloxone were similar. These values were similar to the pA2 value for the interaction of ethylketazocine and naloxone determined on control tissues, but significantly different from the pA2 value for morphine-naloxone on control tissues, indicating that the agonist actions of morphine on preparations pretreated with high concentrations of beta-FNA are mediated by kappa-, rather than mu-receptor interaction. On the mouse vas deferens preparation, co-incubation with the highly selective delta-agonist Tyr-D-Ser-Gly-Phe-Leu-Thr (DSLET) and the non-selective non-equilibrium opiate antagonist beta-chlornaltrexamine (beta-CNA) resulted in marked inhibition of the agonist actions of morphine but had no effect upon the agonist actions of the delta-agonist leucine-enkephalin. The pA2 values for the interactions of naloxone with leucine-enkephalin and etorphine were unaltered by pretreatment with beta-CNA and DSLET. In similarly pretreated tissues, the agonist actions of ethylketazocine were markedly inhibited. It is concluded that manipulation of the guinea-pig ileum and mouse vas deferens preparations in the described manner results in assay systems that possess a largely homogeneous receptor population, and as such are valuable tools with which to evaluate opioid activity.
mesh_terms: D000818:Animals; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D016314:Ethylketocyclazocine; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011957:Receptors, Opioid / Q000032:analysis* / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D016314:Ethylketocyclazocine; D009271:Naltrexone; C017120:chlornaltrexamine; C024524:beta-funaltrexamine; D009020:Morphine; D003496:Cyclazocine