Abstract
THE major active ingredient of marijuana, Δ9-tetrahydrocannabi-nol (Δ9-THC), has been used as a psychoactive agent for thousands of years. Marijuana, and Δ9-THC, also exert a wide range of other effects including analgesia, anti-inflammation, immunosuppression, anticonvulsion, alleviation of intraocular pressure in glaucoma, and attenuation of vomiting1. The clinical application of cannabinoids has, however, been limited by their psychoactive effects, and this has led to interest in the biochemical bases of their action. Progress stemmed initially from the synthesis of potent derivatives of δ9-THC4,5, and more recently from the cloning of a gene encoding a G-protein-coupled receptor for cannabinoids6. This receptor is expressed in the brain but not in the periphery, except for a low level in testes. It has been proposed that the non-psychoactive effects of cannabinoids are either mediated centrally or through direct interaction with other, non-receptor proteins1,7,8. Here we report the cloning of a receptor for cannabinoids that is not expressed in the brain but rather in macrophages in the marginal zone of spleen.
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References
Dewey, W. L. Pharmac. Rev. 38, 151–178 (1986).
Howlett, A. C. et al. Trends Neurosci. 13, 420–432 (1990).
Hollister, L. E. Pharmac. Rev. 38, 1–20 (1986).
Razdan, R. K. Pharmac. Rev. 38, 75–149 (1986).
Devane, W. A., Dysarz, F. A., Johnson, M. R., Melvin, L. S. & Howlett, A. C. Molec. Pharmacol. 34, 605–613 (1988).
Matsuda, L. A., Lolait, S. J., Brownstein, B. J., Young, A. C. & Bonner, T. I. Nature 356, 561–564 (1990).
Martin, B. R. Pharmac. Rev. 38, 45–74 (1986).
Reichman, M., Nen, W. & Hokin, L. E. Molec. Pharmac. 40, 547–555 (1991).
Collins, S. J. Blood 70, 1233–1244 (1987).
Lee, J. et al. J. biol. Chem. 267, 16283–16287 (1992).
Zhou, Q. Y. et al. Proc. natn. Acad. Sci. U.S.A. 89, 7432–7436 (1992).
Baldwin, J. M. EMBO J. 12, 1693–1703 (1993).
Jansen, E. M., Haycock, D. A., Ward, S. J. & Seybold V. S. Brain Res. 575, 93–102 (1992).
Devane, W. A. et al. J. med. Chem. 35, 2065–2069 (1992).
Herkenham, M. et al. Proc. natn. Acad. Sci. U.SA. 87, 1932–1936 (1990).
Devane, W. A. et al. Science 258, 1946–1949 (1992).
Sheets, M. D., Ogg, S. C. & Wickens, M. P. Nucleic. Acids Res. 18, 5799–5805 (1990).
Mailleux, P. & Vanderhaeghen, J.-J. Neuroscience 48, 655–668 (1992).
Kraal, G. Int. Rev. Cytol. 132, 31–74 (1992).
Humphrey, J. H. & Grennan, D. Eur. J. Immun. 11, 221–228 (1981).
Keshav, S., Chung, P., Milon, G. & Gordon, S. J. exp. Med. 174, 1049–1058 (1991).
Conklin, B. R. & Bourne, H. R. Cell 73, 631–641 (1993).
Munson, A. E. & Fehr, K. O. in Adverse Health and Behavioral Consequences of Cannabis Use (eds Fehr, K. O. & Kalant H.) 257–353 (Addiction Research Foundation, Toronto, 1983).
Schatz, A. R., Kessler, F. K. & Kaminski, N. E. Life Sci. 51, 25–30 (1992).
Lopez-Cepero, M., Friedman, M., Klein, T. & Friedman, H. J. Leukocyte Biol. 39, 679–686 (1986).
Hollister, L. E. J. Psychoactive Drugs 24, 159–164 (1992).
Fride, E. & Mechoulam, R. Eur. J. Pharmac. 231, 313–314 (1993).
Gerard, C. M., Mollereau, C., Vassart, G. & Parmentier, M. Biochem. J. 279, 129–134 (1991).
Simmons, D., Makgoba, M. W. & Seed, B. Nature 331, 624–627 (1988).
Seed, B. Nature 329, 840–842 (1987).
Robinson, A. P., White, T. M. & Mason, D. W. Immunology 57, 239–247 (1986).
Dallman, M. J., Thomas, M. L. & Green, J. R. Eur. J. Immun. 12, 511–518 (1982).
Shirasawa, T., Sakamoto, K., Akashi, T., Takahashi, H. & Kawashima, A. Nucleic Acids Res. 20, 909 (1992).
Wisden, W., Morris, B. J. & Hunt, S. P. in Molecular Neurobiology: a Practical Approach (eds Chad, J. & Wheal, H.) 205–225 (IRL at Oxford Univ. Press, Oxford, 1991).
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Munro, S., Thomas, K. & Abu-Shaar, M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 365, 61–65 (1993). https://doi.org/10.1038/365061a0
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DOI: https://doi.org/10.1038/365061a0
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