Titre : | Endogenous formation of morphine in human cells |
Titre traduit : | (La formantion endogène de morphine dans les cellules humaines) |
Auteurs : | POEAKNAPO C. ; J. SCHMIDT ; BRANDSCH M. ; DRAGER B. ; M. H. ZENK |
Type de document : | Périodique |
Année de publication : | 2004 |
Format : | 14091-14095 |
Note générale : |
Proceedings of the National Academy of Sciences of the United States of America, 2004, 101, (39), 14091-14095 |
Langues: | Français |
Discipline : | PRO (Produits, mode d'action, méthode de dépistage / Substances, action mode, screening methods) |
Mots-clés : |
Thésaurus mots-clés MORPHINE ; CHIMIE ; BIOLOGIE |
Résumé : |
ENGLISH : Morphine is a plant (opium poppy)-derived alkaloid and one of the strongest known analgesic compounds. Studies from several laboratories have suggested that animal and human tissue or fluids contain trace amounts of morphine. Its origin in mammals has been believed to be of dietary origin. Here, we address the question of whether morphine is of endogenous origin or derived from exogenous sources. Benzylisoquinoline alkaloids present in human neuroblastoma cells (SH-SY5Y) and human pancreas carcinoma cells (DAN-G) were identified by GC/tandem MS (MS/MS) as norlaudanosoline (DAN-G), reticuline (DAN-G and SH-SY5Y), and morphine (10 nM, SH-SY5Y). The stereochemistry of reticuline was determined to be 1-(S). Growth of the SH-SY5Y cell line in the presence of (18)O2 led to the [(18)O]-labeled morphine that had the molecular weight 4 mass units higher than if grown in (16)O2, indicating the presence of two atoms of (18)O per molecule of morphine. Growth of DAN-G cells in an (18)O2 atmosphere yielded norlaudanosoline and (S)-reticuline, both labeled at only two of the four oxygen atoms. This result clearly demonstrates that all three alkaloids are of biosynthetic origin and suggests that norlaudanosoline and (S)-reticuline are endogenous precursors of morphine. Feeding of [ring-(13)C(6)]-tyramine, [1-(13)C, N-(13)CH3]-(S)-reticuline and [N-CD3]-thebaine to the neuroblastoma cells led each to the position-specific labeling of morphine, as established by GC/MS/MS. Without doubt, human cells can produce the alkaloid morphine. The studies presented here serve as a platform for the exploration of the function of "endogenous morphine" in the neurosciences and immunosciences. |
Domaine : | Drogues illicites / Illicit drugs |
Refs biblio. : | 30 |
Affiliation : |
Biocenter, Martin Luther University Halle-Wittenberg, Weinbergweg 22, 06120 Halle Allemagne. Germany. |
Numéro Toxibase : | 1301622 |
Centre Emetteur : | 13 OFDT |
Cote : | A02780 |
Lien : | http://www.pnas.org/cgi/content/full/101/39/14091 |
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