Evidence for the interaction of morphine with kappa and delta opioid receptors to induce analgesia in beta-funaltrexamine-treated mice.
Mice were treated with increasing doses of beta-funaltrexamine (beta-FNA) ranging from 0.15 to 9.6 nmol i.c.v. in an attempt to substantially reduce the population of mu opioid receptors. Two hours later, the analgesic effect of morphine was assessed by the acetic acid writhing assay. ED50 of morphine [0.97 (0.58-1.60) nmol] was increased 2- and 8.5-fold at the lowest and highest dose of beta-FNA, respectively. When the highest dose was injected twice 24 hr apart and the mice were tested 24 hr after the second dose, the ED50 of morphine had increased 30.5-fold when compared with the control value. The latter beta-FNA-treated mice exhibited an apparent pA2 value of 6.19 (6.10-6.28) for morphine-naloxone compared with the control value of 7.39 (7.05-7.73), suggesting that morphine was interacting with receptors other than mu. Selective kappa (binaltorphimine) and delta (ICI 154129 and ICI 174864) antagonists were used to see whether these other receptors might be involved in mediating morphine analgesia in beta-FNA-treated animals. Because both the kappa and delta antagonists inhibited significantly the analgesic effect of morphine in beta-FNA-treated mice at doses that had no effect on morphine analgesia in control mice, these data suggest that morphine interacts with both kappa and delta receptors to produce analgesia when the population of functional mu receptors is drastically reduced by alkylation with beta-FNA.
Takemori
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AE
Department of Pharmacology, Medical School, University of Minnesota, Minneapolis.
Portoghese
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PS
D000698:Analgesia; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine