Reducing and oxidizing agents sensitize heat-activated vanilloid receptor (TRPV1) current
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
16614139
DOI
10.1124/mol.106.023069
PII: S0026-895X(24)04068-9
Knihovny.cz E-zdroje
- MeSH
- buněčné linie MeSH
- diamid farmakologie MeSH
- dithiothreitol farmakologie MeSH
- ethylmaleimid farmakologie MeSH
- kapsaicin farmakologie MeSH
- kationtové kanály TRPV genetika fyziologie MeSH
- krysa rodu Rattus MeSH
- kyselina dithionitrobenzoová farmakologie MeSH
- lidé MeSH
- membránové potenciály účinky léků MeSH
- metoda terčíkového zámku MeSH
- missense mutace genetika MeSH
- mutace genetika MeSH
- mutantní proteiny genetika fyziologie MeSH
- oxidancia farmakologie MeSH
- peroxid vodíku farmakologie MeSH
- redukční činidla farmakologie MeSH
- sulfhydrylová reagencia farmakologie MeSH
- transfekce MeSH
- vysoká teplota * MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- diamid MeSH
- dithiothreitol MeSH
- ethylmaleimid MeSH
- kapsaicin MeSH
- kationtové kanály TRPV MeSH
- kyselina dithionitrobenzoová MeSH
- mutantní proteiny MeSH
- oxidancia MeSH
- peroxid vodíku MeSH
- redukční činidla MeSH
- sulfhydrylová reagencia MeSH
- Trpv1 protein, rat MeSH Prohlížeč
We have previously reported that the reducing agent dithiothreitol (DTT) strongly increases thermally induced activity of the transient receptor potential vanilloid receptor-1 (TRPV1) channel. Here, we show that exposure to oxidizing agents also enhances the heat-induced activation of TRPV1. The actions of sulfhydryl modifiers on heat-evoked whole-cell membrane currents were examined in TRPV1-transfected human embryonic kidney 293T cells. The sensitizing effects of the membrane-permeable oxidizing agents diamide (1 mM), chloramine-T (1 mM), and the copper-o-complex (100:400 microM) were not reversed by washout, consistent with the stable nature of covalently modified sulfhydryl groups. In contrast, the membrane-impermeable cysteine-specific oxidant 5,5'-dithio-bis-(2-nitrobenzoic acid) (0.5 mM) was ineffective. The alkylating agent N-ethylmaleimide (1 mM) strongly and irreversibly affected heat-evoked responses in a manner that depended on DTT pretreatment. Extracellular application of the membrane-impermeable reducing agent glutathione (10 mM) mimicked the effects of 10 mM DTT in potentiating the heat-induced and voltage-induced membrane currents. Using site-directed mutagenesis, we identified Cys621 as the residue responsible for the extracellular modulation of TRPV1 by reducing agents. These data suggest that the vanilloid receptor is targeted by redox-active substances that directly modulate channel activity at sites located extracellularly as well as within the cytoplasmic domains. The results obtained demonstrate that an optimal redox state is crucial for the proper functioning of the TRPV1 channel and both its reduced and oxidized states can result in an increase in responsiveness to thermal stimuli.
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