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Les récepteurs des opioïdes

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Douleur et Analgésie

Résumé

La mise en évidence des sites de liaison pour les opiacés exogènes a conduit à la découverte des endomorphines. Ces peptides morphinomimétiques endogènes, au nombre d’une vingtaine, appartiennent à trois familles distinctes. A l’hétérogénéité des endomorphines pourrait correspondre la multiplicité des récepteurs des opioïdes actuellement désignés par les lettres grecques μ, δ, κ et ε. Cette distinction en sous-classes, qui reposait initialement sur des données pharmacologiques et biochimiques, est maintenant plainement confirmée par la purification d’entités moléculaires distinctes correspondant aux diverses catégories de récepteurs des opioïdes. Les distributions respectives des récepteurs μ, δ et κ dans le système nerveux sont très différentes, et aucune ne recouvre exactement celle de telle ou telle famille de neurones endomorphiniques. Les progrès récents dans la connaissance des récepteurs des opioïdes suscitent peut-être plus d’interrogations que de certitudes quant aux rôles de ces récepteurs et de leurs ligands endogènes dans diverses fonctions, en particulier la nociception.

Summary

The presence of specific binding sites for exogenous opiates in the central nervous system has led to the discovery of endomorphins. About twenty endogenous opoid peptides, which belong to three distinct families, have been identified so far. To the endomorphin heterogeneity may correspond the multiplicity of the opioid receptors called μ, δ, κ and ε. This subclassification, which derived initially from pharmacological and biochemical studies, is presently fully confirmed by the purification of different molecular entities corresponding to the various types of opioid receptors. The distributions in the nervous system of μ, δ and κ opioid receptors, now reexamined using the new probes available, are distinct, but none of them corresponds exactly to the distribution of endomorphinergic neurones. The most recent advances in opioid receptor field are perhaps more challenging than leading to definitive conclusions about the possible physiological roles of opioid receptors and their endogenous ligands in various functions including nociception.

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Bibliographie

  1. Abood M. E., Law P. Y., Evans C., Loh H. H., Barchas J. andEberwine J.: Regulation of a clone which results in the expression of the δ-opioid receptor. International Narcotics Research Conference, Adelaäide, résumé 028, 1987.

  2. Atweh S. F. andKuhar M. J.: Autoradiographic localization of opiate receptors in rat brain. I. Spinal cord and lower medulla. Brain Res.124, 53–67, 1977.

    Article  PubMed  CAS  Google Scholar 

  3. Atweh S. F. andKuhar M. J.: Distribution and physiological significance of opioid receptors in the brain.Brit. Med. Bull. 39, 47–52, 1983.

    PubMed  CAS  Google Scholar 

  4. Bowen W. D., Gentleman S., Herkenham M. andPert C. B.: Interconverting μ and δ forms of the opiate receptor in rat striatal patches.Proc. Natl. Acad. Sci. (USA)78, 4818–4822, 1981.

    Article  CAS  Google Scholar 

  5. Castanas E., Blanc D., Bourhim N., Cupo A., Cantau P. andGiraud P.: Reassesment of opioid binding sites in the rat brain.Neuropeptides 7, 369–380, 1986.

    Article  PubMed  CAS  Google Scholar 

  6. Cesselin F.: Endomorphines et nociception.Rev. Neurol. 142, 649–670, 1986.

    PubMed  CAS  Google Scholar 

  7. Chaillet P., Coulaud A., Zajac J. M., Fournié-Zaluski M. C., Costentin J. andRoques, B. P.: The μ rather than the δ subtype of opioid receptors appears to be involved in enkephalin induced analgesia.Eur. J. Pharmacol. 101, 83–90, 1984.

    Article  PubMed  CAS  Google Scholar 

  8. Chang K. J., Wei E. T., Killian A. andChang J. K.: Potent morphiceptin analogs: structure activity relationships and morphine-like activities.J. Pharmacol. Exp. Ther. 227, 403–410, 1983.

    PubMed  CAS  Google Scholar 

  9. Cho T. M., Hasegawa J., Ge B. L. andLoh H. H.: Purification to apparent homogeneity of a μ-type opioid receptor from rat brain.Proc. Natl. Acad. Sci. (USA)83, 4138–4142, 1986.

    Article  CAS  Google Scholar 

  10. Cohen M. L., Shuman R. T., Osborne J. J. andGesellchen P. D.: Opioid agonist activity of ICI 174864 and its carboxypeptidase degradation product, LY281217.J. Pharmacol. Exp. Ther. 238, 769–772, 1986.

    PubMed  CAS  Google Scholar 

  11. Corbett A. D., Gillan M. G. C., Kosterlitz H. W., Mc Knight A. T., Paterson S. J. andRobson L. E.: Selectivities of opioid peptide analogues as agonists and antagonists at the δ-receptor.Brit. J. Pharmacol. 83, 271–279, 1984.

    CAS  Google Scholar 

  12. Cotton R., Gilés M. G., Miller L., Shaw J. S. andTimms D.: ICI 174, 864: a highly selective antagonist for the opioid δ-receptor.Eur. J. Pharmacol. 97, 331–332, 1984.

    Article  PubMed  CAS  Google Scholar 

  13. Cruz L. andBasbaum A. I.: Multiple opioid peptides and the modulation of pain: immunohistochemical analysis of dynorphin and enkephalin in the trigeminal nucleus caudalis and spinal cord of the cat.J. Comp. Neurol. 240, 331–348, 1985.

    Article  PubMed  CAS  Google Scholar 

  14. D’Amato R. andHoladay J. W.: Multiple opioid receptors in endotoxic shock: evidence for δ involvement and μ-δ interactionsin vivo.Proc. Natl. Acad. Sci. (USA)81, 2898–2901, 1984.

    Article  CAS  Google Scholar 

  15. Dickenson A. H. andKnox R. J.: Antagonism of μ-opioid receptor-mediated inhibitions of nociceptive neurones by U 50488H and dynorphin A1–13 in the rat dorsal horn.Neurosci. Lett. 75, 229–234, 1987.

    Article  PubMed  CAS  Google Scholar 

  16. Fields H. L., Emson P. C., Leigh B. K., Gilbert R. F. T. andIversen L. L.: Multiple opiate receptor sites on primary afferent fibres.Nature (Londres) 284, 351–353, 1980.

    Article  CAS  Google Scholar 

  17. Gairin J. E., Gouarderes C., Mazarguil H., Alvinerie P. andCros J.: [D-Pro10]dynorphin-1-11) is a highly potent and selective ligand for κ opioid receptors.Eur. J. Pharmacol. 106, 457–458, 1985.

    Article  Google Scholar 

  18. Gouarderes C., Cros J. andQuirion R.: Autoradiographic localization of mu, delta and kappa opioid receptor binding sites in rat and guinea pig spinal cord.Neuropeptides 6, 331–342, 1985.

    Article  PubMed  CAS  Google Scholar 

  19. Hamel E. andBeaudet A.: Electron microscopic autoradiographic localization of opioid receptors in rat neostriatum.Nature (Londres)312, 155–157, 1984.

    Article  CAS  Google Scholar 

  20. Hammonds R. C. Jr.,Nicolas P. andLi C. H.: Betaendorphin-(1–27) is an antagonist of β-endorphin analgesia.Proc. Natl. Acad. Sci. (USA)81, 1389–1390, 1984.

    Article  CAS  Google Scholar 

  21. Hazum E., Chang K. J. andCuatrecasas P.: Specific nonopiate receptors for β-endorphin.Science 205, 1033–1035, 1979.

    Article  PubMed  CAS  Google Scholar 

  22. Howard A. D., de la Baume S., Gioannini T. L., Hiller J. M. andSimon E. J.: Covalent labelling of opioid receptors with radioiodinated human β-endorphin. Identification of bindings subunits.J. Biol. Chem. 260, 10833–10839, 1985.

    PubMed  CAS  Google Scholar 

  23. Hughes J., Smith T. W., Kosterlitz H. W., Fothergill L. A., Morgan B. A. andMorris H. R.: Identification of two related pentapeptides from the brain with potent opiate agonist actions.Nature (Londres)258, 577–579, 1975.

    Article  CAS  Google Scholar 

  24. Hunt S. P., Kelly J. S. andEmson P. C.: The electron microscopic localization of methionine enkephalin within the superificial layers (I and II) of the spinal cord.Neuroscience 5, 1871–1890, 1980.

    Article  PubMed  CAS  Google Scholar 

  25. Illes P., Zieglgansberger W. andHerz A.: Lack of cross-tolerance between morphine and Leu-enkephalin in the mouse vas deferens.Brain Research 197, 260–263, 1980.

    Article  PubMed  CAS  Google Scholar 

  26. Itzhak Y., Hiller J. M. andSimon E. J.: Solubilization and characterization of μ, δ and κ opioid binding sites from guinea pig brain: physical separation of κ receptors.Proc. Natl. Acad. Sci. (USA)81, 4217–4221, 1984.

    Article  CAS  Google Scholar 

  27. Itzhak Y. andSimon E. J.: A novel phencyclidine analog interacts selectively with mu opioid receptors.J. Pharmacol. Exp. Ther. 230, 383–386, 1984.

    PubMed  CAS  Google Scholar 

  28. James I. F., Fischli W. andGoldstein A.: Opioid receptor selectivity of dynorphin gene products.J. Pharmacol. Exp. Ther. 228, 88–93, 1984.

    PubMed  CAS  Google Scholar 

  29. Jessell T. M. andIversen L. L.: Opiate analgesics inhibit substance P release from rat trigeminal nucleus.Nature (Londres)268, 549–551, 1977.

    Article  CAS  Google Scholar 

  30. Khachaturian H., Lewis M. E., Schafer, M. K. H. andWatson S. J.: Anatomy of the CNS opioid systems.Trends Neurosci 111–119, 1985.

  31. Lahti R. A., Mickelson M. M., McCall J. M. andVon Voigtlander P. F.: [3H]U-69593 a highly selective ligand for the opioid κ receptor.Eur. J. Pharmacol. 109, 281–284, 1985.

    Article  PubMed  CAS  Google Scholar 

  32. Li C. H. andChung D.: Isolation and structure of an untriakontrapeptide with opiate activity from camel pituitary glands.Proc. Natl. Acad. Sci. (USA)73, 1145–1148, 1976.

    Article  CAS  Google Scholar 

  33. Lutz R. A., Cruciani R. A., Munson P. J. andRodbard D.: Mu1: a very high affinity subtype of enkephalin binding sites in rat brain.Life Sci. 36, 2233–2238, 1985.

    Article  PubMed  CAS  Google Scholar 

  34. Maneckjee R., Zukin R. S., Archer S., Michael J. andOsei-Gyimah P.: Purification and characterization of the μ opiate receptor from rat brain using affinity chromatography.Proc. Natl. Acad. Sci. (USA)82, 594–598, 1985.

    Article  CAS  Google Scholar 

  35. Martin W. R., Eades C. G., Thompson J. A., Huppler R. E. andGilbert P. E.: The effects of morphine-and naloxone-like drugs in the nondependent and morphine dependent chronic spinal dog.J. Pharmacol. Exp. Ther. 197, 517–532, 1976.

    PubMed  CAS  Google Scholar 

  36. Mauborgne A., Lutz O., Legrand J. C., Hamon M. andCesselin F.: Opposite effects of δ and μ opioid receptor agonists on thein vitro release of substance P-like material from the rat spinal cord.J. Neurochem. 48, 529–537, 1987.

    Article  PubMed  CAS  Google Scholar 

  37. Meunier J. C., Kouakou A., Puget A. andMoisand C.: Multiple opiate binding sites in the central nervous system of the rabbit. Large predominance of a mu subtype in the cerebellum and characterization of the kappa subtype in the thalamus.Mol. Pharmacol. 24, 23–29, 1983.

    PubMed  CAS  Google Scholar 

  38. Mosberg H. I. Hurst R., Hruby V. J., Gee K., Yamamura H. I., Galligan J. J. andBurks T. F.: Bis-penicillamine enkephalins possess highly improved specificity toward δ-opioid receptors.Proc. Natl. Acad. Sci (USA)80, 5871–5874, 1983.

    Article  CAS  Google Scholar 

  39. Newmann E. L. andBarnard E. A.: Identification of an opioid receptor subunit carrying the μ binding site.Biochemistry 23, 5385–5389, 1984.

    Article  Google Scholar 

  40. North R. A.: Opioid receptor types and membrane ions channels.Trends Neurosci., 114–117, 1986.

  41. Pasternak G. W., Simantov R. andSnyder S. H.: Characterization of an endogenous morphine-like factor (enkephalin) in mammalian brain.Mol. Pharmacol. 12, 504–513, 1976.

    PubMed  CAS  Google Scholar 

  42. Pert C. B. andSnyder S. H.: Opiate receptor: demonstration in nervous tissue.Science 179, 1011–1014, 1973.

    Article  PubMed  CAS  Google Scholar 

  43. Portoghese P. S. andTakemori A. E.:Tena: a selective kappa opioid receptor antagonist.Life Sci. 36, 801–805, 1985.

    Article  PubMed  CAS  Google Scholar 

  44. Quirion R., Dimaggio D. A., French E. D., Contreras P. C., Shiloach J., Pert C. B., Everist H., Pert A. andO’Donohue T.: Evidence for an endogenous peptide ligand for the phencyclidine receptor.Peptides 5, 967–973, 1984.

    Article  PubMed  CAS  Google Scholar 

  45. Quirion R. andWeiss A. J.: Peptide E and other proenkephalin-derived peptides are potent kappa opiate receptor agonists.Peptides 4, 445–449, 1983.

    Article  PubMed  CAS  Google Scholar 

  46. Robson L. E., Foote R. W., Maurer R. andKosterlitz H. W.: Opioid binding sites of the κ-type in guinea-pig cerebellum.Neuroscience 12, 621–627, 1984.

    Article  PubMed  CAS  Google Scholar 

  47. Robson L. E. andKosterlitz H. W.: Specific protection of the binding sites of D-Ala2-D-Leu5-enkephalin (δ-receptors) and dihydromorphine (μ-receptors).Proc. R. Soc. Lond. 205, 425–432, 1979.

    Article  CAS  Google Scholar 

  48. Romer D., Buscher H. H., Hill R. C., Maurer R., Petcher T. J., Zeugner H., Benson W., Finner E., Milkowski W. andThies P. W.: Unexpected opioid activity in a known class of drug.Life Sci. 31, 1217–1220, 1982.

    Article  PubMed  CAS  Google Scholar 

  49. Roques B. P.: Pharmacologie des différentes classes de récepteurs opioïdes cérébraux.Rec. Mec. Vet. 162, 1321–1331, 1986.

    CAS  Google Scholar 

  50. Roy S., Zhu Y. X., Lee N. M. andLoh H. H.: Immunological characterization of the mu-opioid receptor. International Narcotics Research Conference, Adelaïde, résumé 030, 1987.

  51. Ruda M. S.: Opiates and pain pathways: demonstration of enkephalin synapses on dorsal horn neurons.Science 215, 1523–1525, 1982.

    Article  PubMed  CAS  Google Scholar 

  52. Schmauss C.: Spinal κ-opioid receptor-mediated antinociception is stimulus-specific.Eur. J. Pharmacol. 137, 197–205, 1987.

    Article  PubMed  CAS  Google Scholar 

  53. Schmauss C. andYaksh T. L.:In vivo studies on spinal opiate receptor systems mediating antinociception II. Pharmacological profiles suggesting a differential association of mu, delta and kappa receptors with visceral and cutaneous thermal stimuli in the rat.J. Pharmacol. Exp. Ther. 228, 1–11, 1984.

    PubMed  CAS  Google Scholar 

  54. Shaw J. S., Miller L., Turnbull M. J., Gormley J. J. andMorley J. S.: Selective antagonists at the opiate deltareceptor.Life Sci. 31, 1259–1262, 1982.

    Article  PubMed  CAS  Google Scholar 

  55. Simon E. J., Hiller J. M. andEdelman I.: Stereospecific binding of the potent narcotic analgesic 3H-etorphine to rat brain homogenate.Proc. Natl. Acad. Sci. (USA)70, 1947–1949, 1973.

    Article  CAS  Google Scholar 

  56. Smith C. B., Bennett-Kelly L. andWoods J. H.: Comparison of “selective” opiate receptor antagonists on the isolated mouse vas deferent.Neuropeptides 5, 161–164, 1984.

    Article  PubMed  CAS  Google Scholar 

  57. Spiegel K. andPasternak G. W.: Meptazinol: a novel mu-1 selective opioid analgesic.J. Pharmacol. Exp. Ther. 228, 414–419, 1983.

    Google Scholar 

  58. Su T. P.: Further demonstration of kappa opioid binding sites in the brain: evidence for heterogeneity.J. Pharmacol. Exp. Ther. 232, 144–148, 1985.

    PubMed  CAS  Google Scholar 

  59. Tempel A. andZukin R. S.: Neuroanatomical patterns of the μ, δ and κ opioid receptors of rat brain determined by quantitativein vitro autoradiography.Proc. Natl. Acad. Sci. (USA),84, 4308–4312, 1987.

    Article  CAS  Google Scholar 

  60. Terenius L.: Characteristics of the “receptor” for narcotic analgesics in synaptic plasma membrane fraction from rat brain.Acta Pharmacol. Toxicol. 33, 377–384, 1973.

    CAS  Google Scholar 

  61. Upton N., Sewell R. D. E. andSpencer P. S. J.: Differentiation of potent mu- and kappa-opiate agonists using heat and pressure antinociceptive profiles and combined potency analysis.Eur. J. Pharmacol. 78, 421–425, 1982.

    Article  PubMed  CAS  Google Scholar 

  62. Vaught J. L., Rothman R. B. andWestfall T. C.: Mu and delta receptors: their role in analgesia and in the differential effects of opioid peptides on analgesia.Life Sci. 30, 1443–1455, 1982.

    Article  PubMed  CAS  Google Scholar 

  63. Vonvogtlander P. F., Lahti R. A. andLudens J. H.: U-50488: a selective and structurally novel non-mu(kappa) opioid agonist.J. Pharmacol. Exp. Ther. 224, 7–12, 1983.

    Google Scholar 

  64. Weber E., Esch F. S., Bohlen P., Paterson S., Corbett A. D., Mac Knight A. T., Kosterlitz H. W., Barchas J. D. andEvans C. J.: Metorphamide: isolation, structure and biologic activity of an amidated opioid octapeptide from bovine brain.Proc. Natl. Acad. Sci. (USA)80, 7362–7366, 1983.

    Article  CAS  Google Scholar 

  65. West R. E. andMiller R. J.: Opiates, second messengers and cell response.Brit. Med. Bull. 39, 53–58, 1983.

    PubMed  CAS  Google Scholar 

  66. Wood P. L.: κ-Agonist analgesics: evidence for μ2 and δ opioid receptor antagonism.Drug Devel. Res. 4, 429–435, 1984.

    Article  CAS  Google Scholar 

  67. Wuster M., Schulz R. andHerz A.: Multiple opiate receptors in peripheral tissue preparations.Biochem. Pharmacol. 30, 1883–1887, 1981.

    Article  PubMed  CAS  Google Scholar 

  68. Zajac J. M., Gacel G., Petit F., Dodey P., Rossingnol P. andRoques B. P.: Deltakephalin, Tyr-D-Thr-Gly-Phe-Leu-Thr: a new highly potent and fully specific agonist for opiate δ-receptors.Biochem. Biophys. Res. Commun. 111, 390–397, 1983.

    Article  PubMed  CAS  Google Scholar 

  69. Zajac J. M., Ling N., Rossier J. andRoques B. P.: κ-receptor specificity of [Met5]enkephalyl-Arg-Gly-Leu and [Met5]enkephalyl-Arg-Gly-Leu-Lys.Eur. J. Pharmacol. 90, 147–148, 1983.

    Article  PubMed  CAS  Google Scholar 

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    F. Cesselin

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Cesselin, F. Les récepteurs des opioïdes. Doul. et Analg. 1, 3–10 (1988). https://doi.org/10.1007/BF03007375

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