Anti-nociceptive action of peripheral mu-opioid receptors by G-beta-gamma protein-mediated inhibition of TRPM3 channels

• Verfasst von: Dembla, Sandeep [VerfasserIn]
• Verfasst von: Nuñez-Badinez, Paulina [VerfasserIn]
• Verfasst von: Greffrath, Wolfgang [VerfasserIn]
• Titel: Anti-nociceptive action of peripheral mu-opioid receptors by G-beta-gamma protein-mediated inhibition of TRPM3 channels
• Verf.angabe: 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
• E-Jahr: 2017
• Jahr: 15 August 2017
• Umfang: 32 S.
• Fussnoten: Gesehen am 03.07.2018
• Titel Quelle: Enthalten in: eLife
• Ort Quelle: Cambridge : eLife Sciences Publications, 2012
• Jahr Quelle: 2017
• Band/Heft Quelle: 6(2017) Artikel-Nummer e26280, 32 Seiten
• ISSN Quelle: 2050-084X
• DOI: doi:10.7554/eLife.26280
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1577206932

Abstract

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.