Substance MCS-18 isolated from Helleborus purpurascens is a potent antagonist of the capsaicin receptor, TRPV1, in rat cultured sensory neurons
Language English Country Czech Republic Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19537933
DOI
10.33549/physiolres.931658
PII: 1658
Knihovny.cz E-resources
- MeSH
- Acrolein analogs & derivatives pharmacology MeSH
- Biological Products pharmacology MeSH
- Pain drug therapy metabolism MeSH
- Helleborus * MeSH
- Capsaicin metabolism MeSH
- TRPV Cation Channels antagonists & inhibitors metabolism MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Acids pharmacology MeSH
- Membrane Potentials drug effects MeSH
- Patch-Clamp Techniques MeSH
- Sensory Receptor Cells cytology drug effects metabolism MeSH
- Ganglia, Spinal cytology MeSH
- Calcium metabolism MeSH
- Hot Temperature MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acrolein MeSH
- Biological Products MeSH
- cinnamaldehyde MeSH Browser
- Capsaicin MeSH
- TRPV Cation Channels MeSH
- Acids MeSH
- MCS-18 MeSH Browser
- Trpv1 protein, rat MeSH Browser
- Calcium MeSH
Extracts of Helleborus roots were traditionally used in the Balkan area for their analgesic action. We report that the pure natural product MCS-18 isolated from this source is a potent, specific and reversible antagonist of the capsaicin receptor, TRPV1, expressed in rat dorsal root ganglion (DRG) neurons. TRPV1 is a non-selective cation channel expressed in a subset of cutaneous and visceral sensory nerve endings and activated by noxious heat, acidity and fatty acid metabolites of arachidonic acid, with a decisive role in inflammatory heat hyperalgesia. MCS-18 inhibited the increase in intracellular calcium concentration evoked in DRG neurons by capsaicin (300 nM) and low pH (5.5) but not by heat (43 degrees C). The substance had no effect on the responses mediated by acid-sensing ion channels (ASICs) or the irritant receptor TRPA1. Whole-cell patch-clamp was used to confirm the inhibition of capsaicin-induced currents by MCS-18 which was dose-dependent. The mechanism of inhibition does not require an intact cell, as capsaicin-induced currents were also inhibited in the excised outside-out configuration. The antagonism of the capsaicin and proton action on native TRPV1 by MCS-18 may be of interest for pain therapy.
Department of Physiology and Biophysics Faculty of Biology University of Bucharest Bucharest Romania
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