Abstract
The possibility that morphine could be synthesized in animals has long been considered1 and a pathway in mammalian brain analogous to that in the opium poppy has been proposed2. Substances have been detected in mammalian brain that are recognized by antisera raised against morphine3–7. Recently we reported the presence of three such immunoreactive substances in bovine hypothalamus and adrenal, and in rat brain, and the definitive identification of two of them by gas chromatography-mass spec-trometry as morphine and codeine8. Incorporation of a labelled precursor has demonstrated the biosynthesis of morphine in the opium poppy from tyrosine-derived units9 (see Fig. 1). Intramolecular coupling of reticuline to form salutaridine is the critical step10 that generates the morphine skeleton (morphinan)11 and the stereochemistry of the morphinan series9. We now report the conversion in vivo and in vitro of reticuline to salutaridine by rat liver, but this conversion is not detectable in rat brain and bovine adrenal. This is the first direct demonstration of the synthesis of a morphinan in an animal tissue and also supports the hypothesis that morphine and codeine in brain and adrenal are of endogenous origin.
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References
1. Mavrojannis, M. Comptes rendue Soc. Biol. 55, 1092-1094 (1903). 2. Davis, V. E. & Walsh, M. J. Science 167, 1005-1007 (1970). 3. Gintzler, A. R., Levy, A. & Spector, S. Proc. natn. Acad. Sci. U.S.A. 73, 2132-2136 (1976). 4. Gintzler, A. R., Gershon, M. D. & Spector, S. Science 199, 447-448 (1978). 5. Killian, A. K. et al. Life Sci. 28, 811-817 (1981). 6. Donnerer, J., Oka, K., Brossi, A., Rice, K. C. & Spector, S. Proc. natn. Acad. Sci. U.S.A. 83,4566-4567 (1986). 7. Goldstein, A. et al. Proc. natn. Acad. Sci. U.S.A. 82, 5203-5207 (1985). 8. Weitz, C. J., Lowney, L. I., Faull, K. F., Feistner, G. & Goldstein, A. Proc. natn. Acad. Sci. U.S.A. 83, 9784-9788 (1986). 9. Kirby, G. W. Science 155, 170-173 (1967). 10. Hodges, C. H. & Rapoport, H. Biochemistry 21, 3729-3734 (1982). 11. Barton, D. H. R. et al. J. Chem. Soc. C, 2423-2438 (1965).
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Weitz, C., Faull, K. & Goldstein, A. Synthesis of the skeleton of the morphine molecule by mammalian liver. Nature 330, 674–677 (1987). https://doi.org/10.1038/330674a0
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DOI: https://doi.org/10.1038/330674a0
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