Use of mu and delta opioid peptides of various selectivity gives further evidence of specific involvement of mu opioid receptors in supraspinal analgesia (tail-flick test).
The tail-flick assay in chronic implanted rats was used to test the analgesic potency of agonists selective for mu opioid receptors: [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO), Tyr-D-Ala-Gly-NH(CH2)2-CH(CH3)2 (TRIMU 5) and for delta receptor subtypes: [D-Ser2,Leu5]enkephalyl-Thr6 (DSLET), [D-Thr2,Leu5]enkephalyl-Thr6 (DTLET) and cyclic [D-Pen2,L-Pen5]enkephalin (DPLPE). DAGO produced an analgesic response at a concentration 500 times lower than DPLPE. The relative activity of these compounds was significantly correlated with their affinity for central or peripheral mu receptors but not with their delta receptor affinity. Diffusion studies of tritiated mu and delta agonists showed that after i.c.v. injection, these enkephalin analogues remained essentially localized within supraspinal structures. Taken together these results suggest strongly that the analgesia produced at the supraspinal level by opioid peptides is related to mu receptor stimulation.
Dauge
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Laboratoire de Pharmacologie, UER des Sciences Pharmaceutiques et Biologiques, Paris, France.
Petit
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Rossignol
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Roques
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BP
D000698:Analgesia; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology; D004723:Endorphins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004745:Enkephalins / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
D004723:Endorphins; D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu