Differential interaction patterns of opioid analgesics with µ opioid receptors correlate with ligand-specific voltage sensitivity
- Philipp University of Marburg, Germany
- University of Nottingham, United Kingdom
Abstract
The µ opioid receptor (MOR) is the key target for analgesia, but the application of opioids is accompanied by several issues. There is a wide range of opioid analgesics, differing in their chemical structure and their properties of receptor activation and subsequent effects. A better understanding of ligand-receptor interactions and the resulting effects is important. Here, we calculated the respective binding poses for several opioids and analyzed interaction fingerprints between ligand and receptor. We further corroborated the interactions experimentally by cellular assays. As MOR was observed to display ligand-induced modulation of activity due to changes in membrane potential, we further analyzed the effects of voltage sensitivity on this receptor. Combining in silico and in vitro approaches, we defined discriminating interaction patterns responsible for ligand-specific voltage sensitivity and present new insights into their specific effects on activation of the MOR.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1, 3, 4, 5, 6.
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Author details
Funding
European Commission (H2020-MSCA- 860229)
- Meritxell Canals
United Kingdom Academy of Medical Siences Proffessorship
- Meritxell Canals
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Kirchhofer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Differential interaction patterns of opioid analgesics with µ opioid receptors correlate with ligand-specific voltage sensitivity
eLife 12:e91291.
https://doi.org/10.7554/eLife.91291
