dc.contributor.author
Celik, Melih Özgür
dc.contributor.author
Seitz, Viola
dc.contributor.author
Yergöz, Fatih
dc.contributor.author
Dembla, Sandeep
dc.contributor.author
Blum, Nina Kathleen
dc.contributor.author
Schulz, Stefan
dc.contributor.author
Stein, Christoph
dc.date.accessioned
2023-09-20T11:04:34Z
dc.date.available
2023-09-20T11:04:34Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/40912
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-40633
dc.description.abstract
N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide is a newly-designed pain killer selectively activating G-protein-coupled mu-opioid receptors (MOR) in acidic injured tissues, and therefore devoid of central side effects which are typically elicited at normal pH values in healthy tissues. However, the neuronal mechanisms underlying NFEPP's antinociceptive effects were not examined in detail so far. Voltage-dependent Ca2+ channels (VDCCs) in nociceptive neurons play a major role in the generation and inhibition of pain. In this study, we focused on the effects of NFEPP on calcium currents in rat dorsal root ganglion (DRG) neurons. The inhibitory role of the G-protein subunits G(i/o) and G beta gamma on VDCCs was investigated using the blockers pertussis toxin and gallein, respectively. GTP gamma S binding, calcium signals and MOR phosphorylation were also investigated. All experiments were performed at acidic and normal pH values using NFEPP in comparison to the conventional opioid agonist fentanyl. At low pH, NFEPP produced more efficient G-protein activation in transfected HEK293 cells and significantly reduced VDCCs in depolarized DRG neurons. The latter effect was mediated by G beta gamma subunits, and NFEPP-mediated MOR phosphorylation was pH-dependent. Fentanyl's responses were not affected by pH changes. Our data indicate that NFEPP-induced MOR signaling is more effective at low pH and that the inhibition of calcium channels in DRG neurons underlies NFEPP's antinociceptive actions.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
mu opioid receptor (MOR)
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Modulation of G-protein activation, calcium currents and opioid receptor phosphorylation by the pH-dependent antinociceptive agonist NFEPP
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
1171855
dcterms.bibliographicCitation.doi
10.3389/fnmol.2023.1171855
dcterms.bibliographicCitation.journaltitle
Frontiers in Molecular Neuroscience
dcterms.bibliographicCitation.originalpublishername
Frontiers Media SA
dcterms.bibliographicCitation.volume
16
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
37251645
dcterms.isPartOf.eissn
1662-5099