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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Crotalphine desensitizes TRPA1 ion channels to alleviate inflammatory hyperalgesia

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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.
Número total de Autores: 12
Tipo de documento: Artigo Científico
Fonte: Pain; v. 157, n. 11, p. 2504-2516, NOV 2016.
Citações Web of Science: 11
Resumo

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)

Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
Beneficiário:Hugo Aguirre Armelin
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 08/57898-0 - Instituto Nacional de Ciência e Tecnologia em Toxinas
Beneficiário:Osvaldo Augusto Brazil Esteves Sant'Anna
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 12/51458-4 - Effect of crotalfine on ion channels in sensory neurons
Beneficiário:Yara Cury
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 98/14307-9 - Center for Applied Toxinology
Beneficiário:Hugo Aguirre Armelin
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs