title: Characterization of [3H] oxymorphone binding sites in mouse brain: Quantitative autoradiography in opioid receptor knockout mice.
abstract: Oxymorphone, one of oxycodone's metabolic products, is a potent opioid receptor agonist which is thought to contribute to the analgesic effect of its parent compound and may have high potential abuse liability. Nonetheless, the in vivo pharmacological binding profile of this drug is still unclear. This study uses mice lacking mu (MOP), kappa (KOP) or delta (DOP) opioid receptors as well as mice lacking all three opioid receptors to provide full characterisation of oxymorphone binding sites in the brain. Saturation binding studies using [3H]oxymorphone revealed high affinity binding sites in mouse brain displaying Kd of 1.7nM and Bmax of 147fmol/mg. Furthermore, we performed quantitative autoradiography binding studies using [3H]oxymorphone in mouse brain. The distribution of [3H]oxymorphone binding sites was found to be similar to the selective MOP agonist [3H]DAMGO in the mouse brain. [3H]Oxymorphone binding was completely abolished across the majority of the brain regions in mice lacking MOP as well as in mice lacking all three opioid receptors. DOP and KOP knockout mice retained [3H]oxymorphone binding sites suggesting oxymorphone may not target DOP or KOP. These results confirm that the MOP, and not the DOP or the KOP is the main high affinity binding target for oxymorphone.
authors.affiliation: Faculty of Health and Medical Sciences, AY building, University of Surrey, Guildford, Surrey GU2 7XH UK; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, United States. Electronic address: jihoonyoo@aol.com.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Yoo
authors.affiliation: Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Temesvari krt 62, H-6726 Szeged, Hungary; Institute of Pharmacodynamics and Biopharmacy, University of Szeged, 6720 Zrinyi u. 9, Hungary.
authors.forename: Anna
authors.initials: A
authors.lastname: Borsodi
authors.affiliation: Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Temesvari krt 62, H-6726 Szeged, Hungary.
authors.forename: Géza
authors.initials: G
authors.lastname: Tóth
authors.affiliation: Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Temesvari krt 62, H-6726 Szeged, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Benyhe
authors.affiliation: Institute of Pharmacodynamics and Biopharmacy, University of Szeged, 6720 Zrinyi u. 9, Hungary.
authors.forename: Robert
authors.initials: R
authors.lastname: Gaspar
authors.affiliation: IGBMC, CNRS/INSERM/ULP 1 rue Laurent Fries, BP 10142, Illkirch, Cedex, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Matifas
authors.affiliation: IGBMC, CNRS/INSERM/ULP 1 rue Laurent Fries, BP 10142, Illkirch, Cedex, France; Department of Psychiatry, Douglas Hospital Research Center, School of Medicine, McGill University, Montreal, QC H3A 1A1, Canada.
authors.forename: Brigitte L
authors.initials: BL
authors.lastname: Kieffer
authors.affiliation: Faculty of Health and Medical Sciences, AY building, University of Surrey, Guildford, Surrey GU2 7XH UK; Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Metaxas
authors.affiliation: Faculty of Health and Medical Sciences, AY building, University of Surrey, Guildford, Surrey GU2 7XH UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Kitchen
authors.affiliation: Faculty of Health and Medical Sciences, AY building, University of Surrey, Guildford, Surrey GU2 7XH UK; Institute of Medical and Biomedical Education, St George's University of London, London SW17 0RE, UK. Electronic address: abailey@sgul.ac.uk.
authors.forename: Alexis
authors.initials: A
authors.lastname: Bailey
mesh_terms: D000818:Animals; D001345:Autoradiography / Q000379:methods; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D018345:Mice, Knockout; D010111:Oxymorphone / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000172:deficiency / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000235:genetics / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000235:genetics / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000235:genetics
chemical_list: D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D010111:Oxymorphone
keywords: Autoradiography; Knockout; Mouse; Opioid; [(3)H]Oxymorphone