Yoo, JH; Borsodi, A; Tóth, G; Benyhe, S; Gaspar, R; Matifas, A; Kieffer, BL; Metaxas, A; Kitchen, I; Bailey, A
(2017)
Characterization of [(3)H] oxymorphone binding sites in mouse brain: Quantitative autoradiography in opioid receptor knockout mice.
Neuroscience Letters, 643.
pp. 16-21.
ISSN 1872-7972
https://doi.org/10.1016/j.neulet.2017.02.002
SGUL Authors: Bailey, Alexis
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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 [(3)H]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 [(3)H]oxymorphone in mouse brain. The distribution of [(3)H]oxymorphone binding sites was found to be similar to the selective MOP agonist [(3)H]DAMGO in the mouse brain. [(3)H]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 [(3)H]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.
Item Type: | Article | |||||||||
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Additional Information: | © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||||||
Keywords: | Autoradiography, Knockout, Mouse, Opioid, [(3)H]Oxymorphone, 1109 Neurosciences, 1702 Cognitive Science, 1701 Psychology | |||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Institute of Medical, Biomedical and Allied Health Education (IMBE) Academic Structure > Institute of Medical, Biomedical and Allied Health Education (IMBE) > Centre for Biomedical Education (INMEBE) |
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Journal or Publication Title: | Neuroscience Letters | |||||||||
ISSN: | 1872-7972 | |||||||||
Language: | eng | |||||||||
Publisher License: | Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0 | |||||||||
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PubMed ID: | 28192197 | |||||||||
Go to PubMed abstract | ||||||||||
URI: | https://openaccess.sgul.ac.uk/id/eprint/108747 | |||||||||
Publisher's version: | https://doi.org/10.1016/j.neulet.2017.02.002 |
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