Characterization of methadone receptor subtypes present in human brain and lung tissues |
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Institution: | 1. Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria;2. Department of Pediatrics II, Medical University Innsbruck, Innsbruck, Austria;3. Department of Gynecological Endocrinology and Reproductive Medicine, Medical University of Innsbruck, Innsbruck, Austria;4. Internal Medicine V, Medical University of Innsbruck, Innsbruck, Austria;5. Tyrolean Cancer Research Institute, Innsbruck, Austria;6. Cancer Research Program, Institute of Biomedicine and FICAN West Cancer Centre, University of Turku, Turku, Finland;7. Research Programs Unit, Genome-Scale Biology and Medicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland;8. Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck, Austria;9. Forensic Science Program, The Pennsylvania State University, University Park, PA, USA;10. Department of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Austria;11. Department of Pediatrics I, Medical University Innsbruck, Innsbruck, Austria;1. Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353, Republic of Korea;2. Bio-therapy Human Resources Center, Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Korea |
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Abstract: | In addition to their use in pain control, opioids can function as regulators of tumor cell growth. We have found that the therapeutic opioid, methadone, significantly inhibits the in vitro and in vivo growth of human lung cancer cells, and this effect appears to be mediated by specific, high affinity, non-conventional opioid binding sites. The present study indicates the existence of multiple subtypes of binding sites mediating the peripheral and central nervous system actions of this drug. Pharmacological and biochemical characterizations of the methadone binding sites expressed in human brain and normal lung tissues indicate that these sites are distinct from each other and from other opioid receptor types present on human and rat brain membranes, as well as those expressed in human lung cancer cells. The identification of distinct methadone receptor types in the different tissues could lead to the development of more selective and less toxic drugs targeted toward the tumor Cells. |
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