Different μ receptor subtypes mediate spinal and supraspinal analgesia in mice Journal Article
| Authors: | Paul, D.; Bodnar, R. J.; Gistrak, M. A.; Pasternak, G. W. |
| Article Title: | Different μ receptor subtypes mediate spinal and supraspinal analgesia in mice |
| Abstract: | To examine the relative roles of μ1- and μ2-receptors in spinal and supraspinal analgesia, we assessed the effects of naloxonazine, naloxone, β-funaltrexamine (β-FNA), and ICI-154,129 on tail-flick analgesia produced by intrathecal or intracerebroventricular injections of the highly μ-selective agonist, [D-Ala2,Me-Phe4,Gly(ol)5]enkephalin (DAGO; μ1 and μ2), [D-Ser2,Leu5]enkephalin-Thr6 (DSLET; μ1 and δ), and the selective δ-receptor agonist [D-Pen2,D-Pen5]enkephalin (DPDPE) in mice. Both DAGO and DSLET supraspinal analgesia were mediated through μ1-receptors. Naloxonazine shifted the supraspinal DAGO dose-response curve 4-fold to the right without changing the curve for spinal DAGO. Likewise, naloxonazine pretreatment shifted supraspinal DSLET analgesia 10-fold, whereas spinal DSLET analgesia was not affected. DPDPE analgesia was not antagonized spinally or supraspinally by naloxonazine pretreatment. These findings suggest that DAGO produces analgesia spinally and supraspinally through different sets of μ-receptors. Moreover, at least two distinct receptor subtypes mediated spinal analgesia. First, naloxone inhibited spinal DAGO analgesia more potently than DPDPE analgesia. Second, the irreversible μ-antagonist, β-FNA, blocks spinal DAGO analgesia. Since spinal DAGO was insensitive to naloxonazine, ruling out a μ1 mechanism, these results indicate a role for μ2-receptors. Spinal DAGO analgesia also developed tolerance to morphine far more slowly than supraspinal DAGO analgesia even though μ-receptors mediate both, as indicated by their sensitivity towards β-FNA. Finally, the δ-antagonist ICI-154,129 is a more potent inhibitor of spinal DPDPE analgesia than spinal DAGO analgesia. Thus, δ-receptors mediate spinal DPDPE analgesia. © 1989. |
| Keywords: | nonhuman; mouse; animal; mice; animal experiment; central nervous system; spinal cord; morphine; oligopeptides; analgesia; mu opiate receptor; receptors, opioid, mu; tail flick test; injections, spinal; naloxone; beta funaltrexamine; enkephalin[2,5 dextro penicillamine]; opioid peptides; receptor subtype; injections, intraventricular; enkephalin, ala(2)-mephe(4)-gly(5)-; receptors, opioid, delta; naloxonazine; opioid receptors; subcutaneous drug administration; receptors, opioid; intracerebroventricular drug administration; β-funaltrexamine; male; priority journal; enkephalin derivative; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; enkephalins; enkephalin, d-penicillamine (2,5)-; intrathecal drug administration; leucine enkephalin[2 dextro serine 6 threonine]; tail-flick; ici-154,129; μ1 opioid receptors; μ2 opioid receptors; enkephalin[2 dextro alanine 4 methylphenylalanine 5 methioninol sulfoxide]; n,n diallyltyrosylglycyl alpha (2 aminoethylthio)hydrocinnamoylleucine; anesthesia, spinal |
| Journal Title: | European Journal of Pharmacology |
| Volume: | 168 |
| Issue: | 3 |
| ISSN: | 0014-2999 |
| Publisher: | Elsevier B.V. |
| Date Published: | 1989-09-22 |
| Start Page: | 307 |
| End Page: | 314 |
| Language: | English |
| DOI: | 10.1016/0014-2999(89)90792-9 |
| PUBMED: | 2555205 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 14 April 2020 -- Source: Scopus |
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