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Multiple opiate receptor sites on primary afferent fibres

Abstract

In addition to their actions at supraspinal sites, opiates can act directly at the spinal cord level to produce analgesia1–3. Opiate receptors and enkephalins are found in abundance in the dorsal horn of the spinal cord, in the region of termination of small-diameter primary afferents4–6. Furthermore, there is evidence that exogenously administered opiates or endogenous enkephalins act both on postsynaptic receptors in dorsal horn and presynaptically to block transmitter release from nociceptive primary afferent terminals7–10. The possiblity of these two distinct sites of opiate action in dorsal horn is of particular interest in view of recent evidence for the existence of multiple opiate receptors11–13. On the basis of differences in the rank orders of potency of opiate alkaloids and opoid peptides observed in different tissues, Lord et al.14 have proposed two categories of opiate receptor, μ and δ, and these can be differentiated in binding studies, provided that selective radioglands are used in the appropriate experimental conditions15–18. Here we have used the selective radioligands 3H-morphine (μ sites) and 3H-D-Ala2, D-Leu5-enkephalin (δ sites) to examine directly in rat the distribution and binding characteristics of opiate receptors on dorsal root and in various regions of the adjacent spinal cord. Primary afferent tissue (dorsal root) and dorsal horn were found to contain μ and δ opiate binding sites with a relatively high proportion of μ sites. Partial destruction of small-diameter primary afferents after cutting the sciatic nerve led to a significant reduction in both μ and δ binding sites on dorsal roots, suggesting that both types of opiate receptors may exist on small-diameter primary afferents.

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References

  1. 1

    Yaksh, T. L. & Rudy, J. A. J. Pharmac. exp. Ther. 202, 411–428 (1977).

  2. 2

    Yaskh, T. L. Brain Res. 153, 205–210 (1978).

  3. 3

    Wang, J. K., Nauss, L. A. & Thomas, J. E. Anaesthesiology 50, 149–151 (1979).

  4. 4

    Hökfelt, T., Ljungdahl, A., Terenius, L., Elde, R. & Nilsson, G. Proc. natn. Acad. Sci. U.S.A. 74, 3081–3085 (1977).

  5. 5

    Pert, C. B., Kuhar, M. J. & Snyder, S. H. Life Sci. 16, 1849–1854 (1975).

  6. 6

    Atweh, S. F. & Kuhar, M. J. Brain Res. 124, 53–67 (1977).

  7. 7

    Jessell, T. M. & Iversen, L. L. Nature 268, 549–551 (1977).

  8. 8

    Mudge, A. W., Leeman, S. E. & Fischbach, G. D. Proc. natn. Acad. Sci. U.S.A. 76, 526–530 (1979).

  9. 9

    Duggan, A. W., Hall, J. G. & Headley, P. M. Br. J. Pharmac. 61, 67–76 (1977).

  10. 10

    Le Bars, D., Guilbaud, G., Jurna, I. & Besson, J. M. Brain Res. 98, 261–277 (1976).

  11. 11

    Martin, W. R., Eades, C. G., Thompson, J. A., Huppler, R. E. & Gilbert, P. E. J. Pharmac. exp. Ther. 197, 517–532 (1976).

  12. 12

    Terenius, L. Psychoneuroendocrinology 2, 53–58 (1977).

  13. 13

    Waterfield, A. A., Smockum, R. W. J., Hughes, J., Kosterlitz, H. W. & Kosterlitz, H. W. & Henderson, G. Eur. J. Pharmac. 43, 107–116 (1977).

  14. 14

    Lord, J. A. H., Waterfield, A. A., Hughes, J. & Kosterlitz, H. W. Nature 267, 495–500 (1977).

  15. 15

    Robson, L. E. & Kosterlitz, H. W. Proc. R. Soc. B205, 425–432 (1979).

  16. 16

    Terenius, L. & Wahlström, A. Eur. J. Pharmac. 40, 241–248 (1976).

  17. 17

    Chang, K-J., Cooper, B. R., Hazum, E. & Cuatrecasas, P. Molec. Pharmac. 16, 91–104 (1979).

  18. 18

    Chang, K-J. & Cuatrecasas, P. J. biol. Chem. 254, 2610–2618 (1979).

  19. 19

    Ranson, S. W. J. comp. Neurol. 16, 265–293 (1906).

  20. 20

    Aldskogius, H. & Arvidsson, J. J. Neurocytol. 7, 229–250 (1978).

  21. 21

    Knyihár, E. & Csillik, B. Expl Brain Res. 26, 73–87 (1976).

  22. 22

    Jessell, T., Tsunoo, A., Kanazawa, I. & Otsuka, M. Brain Res. 168, 247–259 (1979).

  23. 23

    LaMotte, C., Pert, C. B. & Snyder, S. H. Brain Res. 112, 407–412 (1976).

  24. 24

    Atweh, S. F., Murrin, L. C. & Kuhar, M. J. Neuropharmacology 17, 65–71 (1978).

  25. 25

    Jancso, G., Kiraly, E. & Jancso-Gabor, A. Nature 270, 741–743 (1977).

  26. 26

    Gamse, R., Holzer, P. & Lembeck, F. Naunyn-Schmiedebergs Archs Pharmak. 308, 281–285 (1979).

  27. 27

    Nagy, J. I. et al. Brain Res. (in the press).

  28. 28

    Carstens, E., Tulloch, I., Zieglgansberger, W. & Zimmermann, M. Pflügers Arch. ges. Physiol. 379, 143–147 (1979).

  29. 29

    Sastry, B. R. Neuropharmacology 18, 367–375 (1979).

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