Počet záznamů: 1  

Activity dependent inhibition of TRPC1/4/5 channels by duloxetine involves voltage sensor-like domain

  1. 1.
    SYSNO ASEP0559165
    Druh ASEPJ - Článek v odborném periodiku
    Zařazení RIVJ - Článek v odborném periodiku
    Poddruh JČlánek ve WOS
    NázevActivity dependent inhibition of TRPC1/4/5 channels by duloxetine involves voltage sensor-like domain
    Tvůrce(i) Zímová, Lucie (FGU-C) RID, ORCID
    Ptáková, Alexandra (FGU-C)
    Mitro, Michal (FGU-C)
    Krůšek, Jan (FGU-C) RID, ORCID
    Vlachová, Viktorie (FGU-C) RID, ORCID, SAI
    Číslo článku113262
    Zdroj.dok.Biomedicine & Pharmacotherapy. - : Elsevier - ISSN 0753-3322
    Roč. 152, August (2022)
    Poč.str.11 s.
    Jazyk dok.eng - angličtina
    Země vyd.FR - Francie
    Klíč. slovaTRPC channels ; TRPC5 ; Duloxetine ; inhibitor ; voltage sensor-like domain
    Obor OECDPhysiology (including cytology)
    CEPGA22-13750S GA ČR - Grantová agentura ČR
    Způsob publikováníOpen access
    Institucionální podporaFGU-C - RVO:67985823
    UT WOS000815801200004
    EID SCOPUS85132316348
    DOI10.1016/j.biopha.2022.113262
    AnotaceTransient receptor potential canonical 5 (TRPC5) is a polymodal, calcium-permeable, nonselective ion channel that is expressed in the brain and 75 % of human sensory neurons. Its pharmacological or genetic inhibition leads to the relief of neuropathic and inflammatory pain. The clinically approved drug duloxetine is superior to other serotonin and norepinephrine reuptake inhibitors at managing painful neuropathies, but it is not known why. Here we ask whether the TRPC5 receptor is modulated by duloxetine and may contribute to its analgesic effect. Electrophysiological measurements of heterologously expressed human TRPC5 in HEK293T cells were performed to evaluate the effect of duloxetine. The interaction site was identified by molecular docking and molecular dynamics simulations in combination with point mutagenesis. We found that duloxetine inhibits TRPC5 in a concentration-dependent manner with a high potency (IC50 = 0.54 ± 0.03 µM). Our data suggest that duloxetine binds into a voltage sensor-like domain. For the interaction, Glu418 exhibited particular importance due to putative hydrogen bond formation. Duloxetine effectively inhibits TRPC5 currents induced by cooling, voltage, direct agonists and by the stimulation of the PLC pathway. The finding that this TRPC5 inhibitor is widely used and well tolerated provides a scaffold for new pain treatment strategies.
    PracovištěFyziologický ústav
    KontaktLucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400
    Rok sběru2023
    Elektronická adresahttps://doi.org/10.1016/j.biopha.2022.113262
Počet záznamů: 1  

  Tyto stránky využívají soubory cookies, které usnadňují jejich prohlížení. Další informace o tom jak používáme cookies.