Open AccessSubstance MCS-18 Isolated from Helleborus Purpurascens Is a Potent Antagonist of the Capsaicin Receptor, TRPV1, in Rat Cultured Sensory Neurons
Author(s) -
Cristian Neacsu,
Cristian Ciobanu,
I Barbu,
O Toader,
G Szégli,
Franz Kerek,
Alexandru Babeș
Publication year - 2010
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.931658
Subject(s) - trpv1 , capsaicin , chemistry , dorsal root ganglion , pharmacology , antagonist , arachidonic acid , patch clamp , substance p , receptor , biochemistry , transient receptor potential channel , sensory system , biology , neuroscience , neuropeptide , enzyme
Extracts of Helleborus roots were traditionally used in the Balkanarea for their analgesic action. We report that the pure naturalproduct MCS-18 isolated from this source is a potent, specific andreversible antagonist of the capsaicin receptor, TRPV1, expressedin rat dorsal root ganglion (DRG) neurons. TRPV1 is a nonselective cation channel expressed in a subset of cutaneous andvisceral sensory nerve endings and activated by noxious heat,acidity and fatty acid metabolites of arachidonic acid, with adecisive role in inflammatory heat hyperalgesia. MCS-18 inhibitedthe increase in intracellular calcium concentration evoked in DRGneurons by capsaicin (300 nM) and low pH (5.5) but not by heat(43 ºC). The substance had no effect on the responses mediatedby acid-sensing ion channels (ASICs) or the irritant receptorTRPA1. Whole-cell patch-clamp was used to confirm theinhibition of capsaicin-induced currents by MCS-18 which wasdose-dependent. The mechanism of inhibition does not requirean intact cell, as capsaicin-induced currents were also inhibited inthe excised outside-out configuration. The antagonism of thecapsaicin and proton action on native TRPV1 by MCS-18 may beof interest for pain therapy.