The mu-opioid activity of kappa-opioid receptor agonist compounds in the guinea pig ileum.
On the basis of their in vivo activity and binding affinity, nalorphine and (-)SKF 10,047 were classified as mixed agonist/antagonist compounds. However, in isolated tissue preparations without a selective antagonist to block their agonist effect, the characterization of these compounds and the determination of their antagonist activity were very difficult. Nor-binaltorphimine, a selective kappa-opioid receptor antagonist, was used in the longitudinal muscle preparations of the guinea pig ileum to block the kappa-agonist activity of nalorphine and (-)SKF 10,047. In the absence of their kappa-agonist activity, we were able to determine the mu-antagonist activity using the mu-selective agonist DAMGO ([D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin). The pA2 values for nalorphine and (-)SKF 10,047 were 7.50 and 7.69, respectively.
Berzetei-Gurske
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SRI International, Department of Neuroscience, Menlo Park, CA 94025.
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D000818:Animals; D016314:Ethylketocyclazocine / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009269:Nalorphine / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D016314:Ethylketocyclazocine; D009271:Naltrexone; C012134:SK&F 10047; D010620:Phenazocine; D009269:Nalorphine