Anti-nociceptive action of peripheral mu-opioid receptors by G-beta-gamma protein-mediated inhibition of TRPM3 channels
Opioids, agonists of µ-opioid receptors (µORs), are the strongest pain killers clinically available. Their action includes a strong central component, which also causes important adverse effects. However, µORs are also found on the peripheral endings of nociceptors and their activation there produce...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
15 August 2017
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| In: |
eLife
Year: 2017, Volume: 6 |
| ISSN: | 2050-084X |
| DOI: | 10.7554/eLife.26280 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.7554/eLife.26280 Verlag, kostenfrei, Volltext: https://elifesciences.org/articles/26280 
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| Author Notes: | Sandeep Dembla, Marc Behrendt, Florian Mohr, Christian Goecke, Julia Sondermann, Franziska M. Schneider, Marlene Schmidt, Julia Stab, Raissa Enzeroth, Michael G. Leitner, Paulina Nuñez-Badinez, Jochen Schwenk, Bernd Nürnberg, Alejandro Cohen, Stephan E. Philipp, Wolfgang Greffrath, Moritz Bünemann, Dominik Oliver, Eleonora Zakharian, Manuela Schmidt, Johannes Oberwinkler |
| Summary: | Opioids, agonists of µ-opioid receptors (µORs), are the strongest pain killers clinically available. Their action includes a strong central component, which also causes important adverse effects. However, µORs are also found on the peripheral endings of nociceptors and their activation there produces meaningful analgesia. The cellular mechanisms downstream of peripheral µORs are not well understood. Here, we show in neurons of murine dorsal root ganglia that pro-nociceptive TRPM3 channels, present in the peripheral parts of nociceptors, are strongly inhibited by µOR activation, much more than other TRP channels in the same compartment, like TRPV1 and TRPA1. Inhibition of TRPM3 channels occurs via a short signaling cascade involving Gβγ proteins, which form a complex with TRPM3. Accordingly, activation of peripheral µORs in vivo strongly attenuates TRPM3-dependent pain. Our data establish TRPM3 inhibition as important consequence of peripheral µOR activation indicating that pharmacologically antagonizing TRPM3 may be a useful analgesic strategy. |
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| Item Description: | Gesehen am 03.07.2018 |
| Physical Description: | Online Resource |
| ISSN: | 2050-084X |
| DOI: | 10.7554/eLife.26280 |