Multiple Opiate Receptors and Their Functional Significance

Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 18)


There is ample evidence from studies of peripheral isolated organs, binding of opiate receptor ligands to brain membranes and behavioural experiments that opiate receptors are not homogeneous but consist of different types such as the μ- (= morphine), δ- (= enkephalin), ϰ- (= ketocyclazocine) and the ε- (= β-endorphin) receptors. In addition, there are indications for subtypes within the particular classes of receptors, at least in the case of μ-land ϰ-receptors. In one organ or particular brain structure, several types of receptors can be present—though big differences in the relative concentrations between various brain areas exist. The precise nature of the relationship between the multiplicity of opiate receptors and the multiplicity of endogenous opioids is not clear. The enkephalins and dynorphin appear to be, however, related to, respectively, δ- and ϰ-receptors. According to our present knowledge, there is no strict relationship between certain physiological functions (or pharmacological actions) and the activation of a particular receptor type; for example, μ-, δ- and ϰ-receptors are involved in pain modulation.


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  1. Bowen, W. D., Gentleman, S., Herkenham, M., Pert, C. B.: Interconventing my and delta forms of the opiate receptor in the rat striatal patches. Proc. Natl. Acad. Sci. U.S.A. 78, 4818–4822 (1981).CrossRefPubMedCentralPubMedGoogle Scholar
  2. Chang, K.J., Cuatrecasas, P.: Multiple opiate receptors: enkephalins and morphine bind to receptors of different specificity. J. Biol. Chem. 254, 2610–2618 (1979).PubMedGoogle Scholar
  3. Chang, K.J., Hazum, L., Cuatrecasas, P.: Novel opiate binding sites, selective for benzomorphan drugs. Proc. Natl. Acad. Sci. U.S.A. 78, 4141–4145 (1981).CrossRefPubMedCentralPubMedGoogle Scholar
  4. Chavkin, Ch., James, I. F., Goldstein, A.: Dynorphin is a specific endogenous ligand of the x-opioid receptor. Science 215, 413–415 (1982).CrossRefPubMedGoogle Scholar
  5. Fields, H.L., Emson, P. C., Leigh, B. K., Gilbert, R.F. T., Iversen, L.L.: Multiple opiate receptors in primary afferent fibres. Nature 284, 351–353 (1980).CrossRefPubMedGoogle Scholar
  6. Kosterlitz, H.A. W., Paterson, S.J., Robson, L.E.: Characterization of the x-subtype of the opiate receptor in the guinea pig brain. Brit. J. Pharmacol. 73, 939–949 (1981).CrossRefGoogle Scholar
  7. Leslie, F. M., Chavkin, C., Cox, B. M.: Opioid binding properties of brain and peripheral tissue: Evidence for heterogeneity in opioid ligand binding sites. J.Pharmacol. exp. Ther. 214, 395–402 (1980).Google Scholar
  8. Lord, J. A., Waterfield, A.A., Hughes, J., Kosterlitz, H. W.: Endogenous opioid peptides: multiple agonists and receptors. Nature 267, 495–499 (1977).CrossRefPubMedGoogle Scholar
  9. Martin, W.R., Eades, C. G., Thompson, J. A., Huppler, R. E., Gilbert, P.E.: The effects of morphine- and nalorphine-like drugs in the nondependent and the morphine-dependent chronic spinal dog. J.Pharmacol. exp. Ther. 197, 517–532 (1976).Google Scholar
  10. Oka, T., Negishi, K., Suda, M., Matsumiya, T., Inazu, T., Ueki, M.: Rabbit vas deferens: A specific bioassay for opioid x-receptors. Europ. J. Pharma-col. 73, 235–236 (1980).CrossRefGoogle Scholar
  11. Pasternak, G. W., Childers, S. R., Snyder, S. H.: Opiate analgesia: Evidence for mediation by a subpopulation of opiate receptors. Science 208, 514–515 (1980).CrossRefPubMedGoogle Scholar
  12. Pfeiffer, A., Herz, A.: Demonstration and distribution of an opiate binding site in rat brain with high affinity for ethylketocyclazocine and SKF 10,047. Biochem. Biophys. Res. Comm. 101, 38–44 (1981).CrossRefPubMedGoogle Scholar
  13. Pfeiffer, A., Pasi, A., Mehraein, P., Herz, A.: A subclassification of x-sites in human brain by use of dynorphin. Neuropeptides 2, 89–97 (1981).CrossRefGoogle Scholar
  14. Pfeffer, A., Herz, A.: Discrimination of 3 opiate binding sites with the use of a computerized curve fitting technique. Molec. Pharmacol. 21, 266–271 (1982).Google Scholar
  15. Pfeiffer, A., Pasi, A., Mehraein, P., Herz, A.: Opiate receptor binding sites in human brain. Brain Res. 248, 87–96 (1982).CrossRefPubMedGoogle Scholar
  16. Schulz, R., Wüster, M., Krenss, H., Herz, A.: Selective development of tolerance without dependence in multiple opiate receptors of mouse vas deferens. Nature 285, 242–243 (1980).CrossRefPubMedGoogle Scholar
  17. Schulz, R., Wüster, M., Krenss, H., Herz, A.: Lack of crosstolerance on multiple opiate receptors in the mouse vas deferens. Molec. Pharmacol. 18, 395–401 (1980).Google Scholar
  18. Schulz, R., Wüster, M.: Are there subtypes (isoreceptors) of multiple opiate receptors in the mouse vas deferens? Europ. J. Pharmacol. 76, 61–66 (1981).Google Scholar
  19. Schulz, R., Wüster, M., Herz, A.: Pharmacological characterization of the c-opiate receptor. J. Pharmacol. exp. Ther. 216, 604–606 (1981).PubMedGoogle Scholar
  20. Schulz, R., Wüster, M., Rubini, P., Herz, A.: Functional opiate receptors in the guinea-pig ileum: their differentiation by means of selective tolerance development. J. Pharmacol. exp. Ther. 219, 547–550 (1981).PubMedGoogle Scholar
  21. Schulz, R., Wüster, M., Herz, A.: Differentiation of opiate receptors in the brain by selective development of tolerance. Pharmacol. Biochem. Behay. 14, 75–79 (1981).CrossRefGoogle Scholar
  22. Shearman, G. T., Herz, A.: Evidence that the different discriminative stimulus properties of fentanyl and ethylketocyclazocine in the rat are mediated by an interaction with different opiate receptors. J. Pharmacol. exp. Ther. 221, 735–739 (1982).PubMedGoogle Scholar
  23. Shearman, G. T., Herz, A.: D-Ala2, D-Leu5-Enkephalin generalizes to a discriminative stimulus produced by fentanyl but not ethylketocyclazocine. Pharmacol. Biochem. Behay. 16, 249–252 (1982).CrossRefGoogle Scholar
  24. Snyder, S. H., Goodman, R. R.: Multiple neurotransmitter receptors. J. Neuro-chem. 35, 5–15 (1980).Google Scholar
  25. Upton, N., Sewell, W., Spencer, P. S.: Differentiations of potent µ- and x-opiate agonists using heat and pressure antinociceptive profiles and combined potency analgesia. Europ. J. Pharmacol. 78, 421–429 (1982).CrossRefGoogle Scholar
  26. Vaught, J. L., Kitano, T., Takemori, A. E.: Interactions of leucine-enkephalin and narcotics with opioid receptors. Mol. Pharmacol. 19, 236–241 (1981).PubMedGoogle Scholar
  27. Williams, J., Zieglgänsberger, W.: Neurones in the frontal cortex of the rat carry multiple opiate receptors. Brain Res. 226, 304–308 (1981).CrossRefPubMedGoogle Scholar
  28. Wood, P. L.: Commentary. Multiple opiate receptors: support for unique my, delta and kappa sites. Neuropharmacology 21, 487–497 (1982).CrossRefPubMedGoogle Scholar
  29. Wood, P. L., Rackham, A., Richard, J.: Spinal analgesia: comparison of the my agonist morphine and the x-agonist ethylketocyclazocine. Life Sci. 28, 2119–2135 (1981).CrossRefPubMedGoogle Scholar
  30. Wüster, M., Schulz, R., Herz, A.: Highly specific opiate receptors for dynorphin (1–13) in the mouse vas deferens. Europ. J. Pharmacol. 62, 235–236 (1980).CrossRefGoogle Scholar
  31. Wüster, M., Schulz, R., Herz, A.: Multiple opiate receptors in peripheral tissue preparations. Biochem. Pharmacol. 30, 1883–1887 (1981).CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 1983

Authors and Affiliations

  • A. Herz
    • 1
  1. 1.Abteilung für NeuropharmakologieMax-Planck-Institut für PsychiatrieMünchen 40Federal Republic of Germany

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