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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Crotalphine desensitizes TRPA1 ion channels to alleviate inflammatory hyperalgesia

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Author(s):
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Bressan, Elisangela ; Touska, Filip ; Vetter, Irina ; Kistner, Katrin ; Kichko, Tatjana I. ; Teixeira, Nathalia B. ; Picolo, Gisele ; Cury, Yara ; Lewis, Richard J. ; Fischer, Michael J. M. ; Zimmermann, Katharina ; Reeh, Peter W.
Total Authors: 12
Document type: Journal article
Source: Pain; v. 157, n. 11, p. 2504-2516, NOV 2016.
Web of Science Citations: 11
Abstract

Crotalphine is a structural analogue to a novel analgesic peptide that was first identified in the crude venom from the South American rattlesnake Crotalus durissus terrificus. Although crotalphine's analgesic effect is well established, its direct mechanism of action remains unresolved. The aim of the present study was to investigate the effect of crotalphine on ion channels in peripheral pain pathways. We found that picomolar concentrations of crotalphine selectively activate heterologously expressed and native TRPA1 ion channels. TRPA1 activation by crotalphine required intact N-terminal cysteine residues and was followed by strong and long-lasting desensitization of the channel. Homologous desensitization of recombinant TRPA1 and heterologous desensitization in cultured dorsal root ganglia neurons was observed. Likewise, crotalphine acted on peptidergic TRPA1-expressing nerve endings ex vivo as demonstrated by suppression of calcitonin gene-related peptide release from the trachea and in vivo by inhibition of chemically induced and inflammatory hypersensitivity in mice. The crotalphine-mediated desensitizing effect was abolished by the TRPA1 blocker HC030031 and absent in TRPA1-deficient mice. Taken together, these results suggest that crotalphine is the first peptide to mediate antinociception selectively and at subnanomolar concentrations by targeting TRPA1 ion channels. (AU)

FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
Grantee:Hugo Aguirre Armelin
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 08/57898-0 - National Institute of Science and Technology on Toxins
Grantee:Osvaldo Augusto Brazil Esteves Sant'Anna
Support type: Research Projects - Thematic Grants
FAPESP's process: 12/51458-4 - Effect of crotalfine on ion channels in sensory neurons
Grantee:Yara Cury
Support type: Regular Research Grants
FAPESP's process: 98/14307-9 - Center for Applied Toxinology
Grantee:Hugo Aguirre Armelin
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC