Crotalphine desensitizes TRPA1 ion channels to alleviate inflammatory hyperalgesia

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F16%3A00470171" target="_blank" >RIV/67985823:_____/16:00470171 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1097/j.pain.0000000000000669" target="_blank" >http://dx.doi.org/10.1097/j.pain.0000000000000669</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1097/j.pain.0000000000000669" target="_blank" >10.1097/j.pain.0000000000000669</a>

Result language

angličtina

Original language name

Crotalphine desensitizes TRPA1 ion channels to alleviate inflammatory hyperalgesia

Original language description

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.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

ED - Physiology

OECD FORD branch

—

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Pain

ISSN

0304-3959

e-ISSN

—

Volume of the periodical

157

Issue of the periodical within the volume

11

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

2504-2516

UT code for WoS article

000386016400016

EID of the result in the Scopus database

2-s2.0-84992563947