Improved assays for the assessment of ϰ- and δ-properties of opioid ligands

Susan J. Ward, P. S. Portoghese, A. E. Takemori

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The highly selective non-equilibrium μ-antagonist β-funaltrexamine (β-FNA) produced a maximal 20-fold shift in the IC50 for the μ-agonist morphine on the guinea-pig ileum preparation, whilst producing no significant change in the IC50 for the κ{script}-agonist ethylketazocine. On preparations pretreated with β-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 concentrationsof β-FNA are mediated by κ{script}-, rather than μ-receptor interaction. On the mouse was deferens preparation, co-incubation with the highly selective δ-agonist Tyr-D-Ser-Gly-Phe-Leu-Thr (DSLET) and the non-selective non-equilibrium opiate antagonist β-chlornaltrexamine (β-CNA) resulted in marked inhibition of the agonist actions of morphine but had no effect upon the agonist actions of the δ-agonist leucine-enkephalin. The pA2 values for the interactions of naloxone with leucine-enkephalin and etorphine were unaltered by pretreatment with β-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.

Original languageEnglish (US)
Pages (from-to)163-170
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number2
StatePublished - Nov 19 1982

Bibliographical note

Funding Information:
For many years, morphine has been the archetypal drug with which to study opiates. Since the discovery of the endogenous opioids (Hughes et al., 1975; Feldberg and Smyth, 1976; Gentleman et al., 1976) and the general acceptance that there exist multiple forms of the opiate receptor * This work was supported by U.S. Public Health Service Grant DA 00289. To whom all correspondence should be addressed: Depart-ment of Pharmacology, University of Minnesota, 435 De-laware Street S.E., 3-260 MiUard Hall, Minneapolis, Min-nesota 55455, U.S.A.


  • Guinea-pig ileum preparation
  • Mouse vas deferens preparation
  • Multiple opioid receptors
  • β-FNA β-CNA


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