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05 May 2005 : Original article  

Advances in Endogenous Morphine

George B. Stefano

Med Sci Monit 2005; 11(5): ED1-1 :: ID: 16132


On January 20 the first International Endogenous Morphine meeting began, sponsored by the National Institutes of Health Fogarty International Center. Present were scientists from 8 countries as well as undergraduate and high school students supported by the National Institute of Mental Health and National Institute on Drug Abuse minority research programs. All were gathered to present their research projects dealing with the demonstration of endogenous morphine and its synthesis in animal tissues, including human. Included in the talks were discussions on the biomedical implications of endogenous morphinergic signaling within various tissues.
Dr. Wei Zhu presented data demonstrating that in vitro incubation of invertebrate ganglia with L-DOPA increases endogenous morphine levels as does whole animal injection of L-DOPA, demonstrating that normal and healthy animals can synthesize morphine from these putative precursors, which are also shared with the catecholamine pathway. Ms. Chotima Poeaknapo, using human neuroblastoma cells (SH-SY5Y) and human pancreas carcinoma (DAN-G) cells demonstrated that morphine, reticuline and norlaudanosoline are unequivocally biosynthesized by cultured human cancer cells. Furthermore, she presented data demonstrating that morphine’s precursors were oxygen, tyramine, reticuline and thebaine in these cancer cell lines. Dr. Else Tønnesen demonstrated that morphine is present in human gliomas, suggesting that it may exert an action that affects tumour physiology/pathology. Dr. Gregory Fricchione presented information concerning endogenous morphine and placebo processes. Dr. Thomas Bilfinger discussed potential involvement of endogenous morphine with ischemic preconditioning in vascular trauma. Dr. Geert Baggermann presented data on the mass spec identification of morphine.
Drs. Patrick Cadet and George B. Stefano discussed data resulting from the acute affects of morphine exposure to human leukocytes by analyzing the expression of different genes via microarray technology. Their study revealed that morphine differentially affected gene expression, which is involved in immune function, signal transduction and cell adhesion, to name a few. Dr. Yannick Goumon demonstrated the presence of morphine 6 glucuronide inside the bovine chromaffin cell secretory granules. This alkaloid was also detected in the secretion medium of primary chromaffin cells in culture following nicotinic stimulation. Kirk Mantione presented information related to morphine 6 glucuronide being a peripheral opiate alkaloid messenger. Dr. Dario Sonetti demonstrated that in mollusks there is a diversified but close association between morphine and ACTH, both acting in a stress response. Furthermore, this relationship also exists in mammals, suggesting that the relationship evolved in invertebrates and was conserved during evolution. Federico Casares presented data on lobster morphinergic processes. Dr. Tobias Esch presented data, which explains the role of endogenous morphine in pleasure and reward circuitry.
Dr. Enrica Bianchi presented her pioneering studies, supporting the hypothesis that she and Dr. Massimo Guarna have been working on that morphine is a central nervous system neurotransmitter. Dr. Stephen Pryor presented data that demonstrates that parasites use and make morphine to escape detection by the mammalian immune system. In this regard, in 2000 Dr. Goumon and colleagues were the first to demonstrate that an animal, i.e., parasite, can make morphine J. Immunol [1].
The meeting closed with the creation of the Morphine Research Society whereby Dr. George B. Stefano was elected as President, Dr. Enrica Bianchi as Vice President, Dr. Dario Sonetti as Treasurer and Dr. Thomas Bilfinger as Secretary. On the whole, the participants support the hypothesis that animals can make morphine.
1.Goumon Y, Casares F, Pryor S et al: Ascaris suum, an internal parasite, produces morphine. J Immunol, 2000; 165: 339–43

Keywords: Morphine - metabolism, Nervous System - metabolism, Morphine - metabolism, Nervous System - metabolism

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750