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Structure of a cannabinoid receptor and functional expression of the cloned cDNA

Nature volume 346, pages 561–564 (1990)Cite this article

Abstract

MARIJUANA and many of its constituent cannabinoids influence the central nervous system (CNS) in a complex and dose-dependent manner1,2. Although CNS depression and analgesia are well documented effects of the cannabinoids, the mechanisms responsible for these and other cannabinoid-induced effects are not so far known3. The hydrophobic nature of these substances has suggested that cannabinoids resemble anaesthetic agents in their action, that is, they nonspecifically disrupt cellular membranes. Recent evidence, however, has supported a mechanism involving a G protein-coupled receptor found in brain and neural cell lines, and which inhibits adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner4–7. Also, the receptor is more responsive to psychoactive cannabinoids than to non-psychoactive cannabinoids8. Here we report the cloning and expression of a complementary DNA that encodes a G protein-coupled receptor with all of these properties. Its messenger RNA is found in cell lines and regions of the brain that have cannabinoid receptors. These findings suggest that this protein is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana.

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References

  1. Hollister, L. E. Pharmac. Rev. 38, 1–20 (1986).

    CAS  Google Scholar 

  2. Martin, B. R. Pharmac. Rev. 38, 45–74 (1986).

    CAS  Google Scholar 

  3. Dewey, W. L. Pharmac. Rev. 38, 151–178 (1986).

    CAS  Google Scholar 

  4. Howlett, A. C. Molec. Pharmacol. 27, 429–436 (1985).

    CAS  Google Scholar 

  5. Howlett, A. C. & Fleming, R. M. Molec. Pharmacol. 26, 532–538 (1984).

    CAS  Google Scholar 

  6. Howlett, A. C., Qualy, J. M. & Khachatrian, L. L. Molec. Pharmacol. 29, 307–313 (1986).

    CAS  Google Scholar 

  7. Devane, W. A., Dysarz, F. A., Johnson, M. R., Melvin, L. S. & Howlett, A. C. Molec. Pharmacol. 34, 605–613 (1988).

    CAS  Google Scholar 

  8. Howlett, A. C. Neuropharmacology 26, 507–512 (1987).

    Article  CAS  Google Scholar 

  9. Bonner, T. I., Buckley, N. J., Young, A. C. & Brann, M. R. Science 237, 527–532 (1987).

    Article  CAS  ADS  Google Scholar 

  10. Nirenburg, M. et al. Science 222, 794–799 (1983).

    Article  ADS  Google Scholar 

  11. Devane, W. A., Spain, J. W., Coscia, C. J. & Howlett, A. C. J. Neurochem. 46, 1925–1935 (1986).

    Google Scholar 

  12. Herkenham, M. et al. Proc. natn. Acad. Scl. U.S.A. 87, 1932–1936 (1990).

    Article  CAS  ADS  Google Scholar 

  13. Bidaut-Russell, M., Devane, W. A. & Howlett, A. C. J. Neurochem. 55, 21–26 (1990).

    Article  CAS  Google Scholar 

  14. Howlett, A. C., Johnson, M. R., Melvin, L. S. & Milne, G. M. Molec. Pharmacol. 33, 297–302 (1988).

    CAS  Google Scholar 

  15. Razdan, R. K. Pharmac. Rev. 38, 75–149 (1986).

    CAS  Google Scholar 

  16. Gilman, A. G. Cell 36, 577–579 (1984).

    Article  CAS  Google Scholar 

  17. Lawrence, D. K. & Gill, E. W. Molec. Pharmacol. 11, 595–602 (1975).

    CAS  Google Scholar 

  18. Hillard, C. J., Harris, R. A. & Bloom, A. S. J. Pharmac. exp. Ther. 232, 579–588 (1985).

    CAS  Google Scholar 

  19. Masu, Y. et al. Nature 329, 836–838 (1987).

    Article  CAS  ADS  Google Scholar 

  20. McFarland, K. C. et al. Science 245, 494–499 (1989).

    Article  CAS  ADS  Google Scholar 

  21. Loosfelt, H. et al. Science 245, 525–528 (1989).

    Article  CAS  ADS  Google Scholar 

  22. Young, D., Waitches, G., Birchmeier, C., Fasano, O. & Wigler, M. Cell 45, 711–719 (1986).

    Article  CAS  Google Scholar 

  23. Karnik, S. S., Sakmar, T. P., Chen, H.-B. & Khorana, H. G. Proc. natn. Acad. Sci. U.S.A. 85, 8459–8463 (1988).

    Article  CAS  ADS  Google Scholar 

  24. Okayama, H. & Berg, P. Molec. cell. Biol. 3, 280–289 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Chomczynski, P. & Sacchi, N. Analyt. Biochem. 162, 156–159 (1987).

    Article  CAS  Google Scholar 

  26. Young, W. S. III, Bonner, T. I. & Brann, M. R. Proc. natn. Acad. Sci. U.S.A. 83, 9827–9831 (1986).

    Article  CAS  ADS  Google Scholar 

  27. Young, W. S. III, Warden, M. & Mezey, E. Neuroendocrinology 46, 439–444 (1987).

    Article  Google Scholar 

  28. Chen, C. & Okayama, H. Molec. cell. Biol. 7, 2745–2752 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Brooker, G., Harper, J. F., Terasaki, W. L. & Moylan, R. D. Adv. Cyclic Nucleotide Res. 10, 1–33 (1979).

    CAS  PubMed  Google Scholar 

  30. Borst, S. & Conolly, M. Life Sci. 43, 1021–1030 (1988).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Cell Biology, National Institutes of Mental Health, Bethesda, Maryland, 20892, USA

    Lisa A. Matsuda, Stephen J. Lolait, Michael J. Brownstein, Alice C. Young & Tom I. Bonner

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  1. Lisa A. Matsuda
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  2. Stephen J. Lolait
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  3. Michael J. Brownstein
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  4. Alice C. Young
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  5. Tom I. Bonner
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Matsuda, L., Lolait, S., Brownstein, M. et al. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346, 561–564 (1990). https://doi.org/10.1038/346561a0

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