Characterization of [3H] oxymorphone binding sites in mouse brain

Quantitative autoradiography in opioid receptor knockout mice

Ji Hoon Yoo, Anna Borsodi, Géza Tóth, Sándor Benyhe, R. Gáspár, Audrey Matifas, Brigitte L. Kieffer, Athanasios Metaxas, Ian Kitchen, Alexis Bailey

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 1.7 nM and Bmax of 147 fmol/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.

Original languageEnglish
Pages (from-to)16-21
Number of pages6
JournalNeuroscience Letters
Volume643
DOIs
Publication statusPublished - Mar 16 2017

Fingerprint

Oxymorphone
Opioid Receptors
Autoradiography
Knockout Mice
Binding Sites
Brain
Ala(2)-MePhe(4)-Gly(5)-enkephalin
Oxycodone
delta Opioid Receptor
Analgesics

Keywords

  • Autoradiography
  • Knockout
  • Mouse
  • Opioid
  • [H]Oxymorphone

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Characterization of [3H] oxymorphone binding sites in mouse brain : Quantitative autoradiography in opioid receptor knockout mice. / Yoo, Ji Hoon; Borsodi, Anna; Tóth, Géza; Benyhe, Sándor; Gáspár, R.; Matifas, Audrey; Kieffer, Brigitte L.; Metaxas, Athanasios; Kitchen, Ian; Bailey, Alexis.

In: Neuroscience Letters, Vol. 643, 16.03.2017, p. 16-21.

Research output: Contribution to journalArticle

Yoo, Ji Hoon ; Borsodi, Anna ; Tóth, Géza ; Benyhe, Sándor ; Gáspár, R. ; Matifas, Audrey ; Kieffer, Brigitte L. ; Metaxas, Athanasios ; Kitchen, Ian ; Bailey, Alexis. / Characterization of [3H] oxymorphone binding sites in mouse brain : Quantitative autoradiography in opioid receptor knockout mice. In: Neuroscience Letters. 2017 ; Vol. 643. pp. 16-21.
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