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TRPA1 is essential for the vascular response to environmental cold exposure

The cold-induced vascular response, consisting of vasoconstriction followed by vasodilatation, is critical for protecting the cutaneous tissues against cold injury. Whilst this physiological reflex response is historic knowledge, the mechanisms involved are unclear. Here by using a murine model of l...

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Autores principales: Aubdool, Aisah A., Graepel, Rabea, Kodji, Xenia, Alawi, Khadija M., Bodkin, Jennifer V., Srivastava, Salil, Gentry, Clive, Heads, Richard, Grant, Andrew D., Fernandes, Elizabeth S., Bevan, Stuart, Brain, Susan D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284811/
https://www.ncbi.nlm.nih.gov/pubmed/25501034
http://dx.doi.org/10.1038/ncomms6732
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author Aubdool, Aisah A.
Graepel, Rabea
Kodji, Xenia
Alawi, Khadija M.
Bodkin, Jennifer V.
Srivastava, Salil
Gentry, Clive
Heads, Richard
Grant, Andrew D.
Fernandes, Elizabeth S.
Bevan, Stuart
Brain, Susan D.
author_facet Aubdool, Aisah A.
Graepel, Rabea
Kodji, Xenia
Alawi, Khadija M.
Bodkin, Jennifer V.
Srivastava, Salil
Gentry, Clive
Heads, Richard
Grant, Andrew D.
Fernandes, Elizabeth S.
Bevan, Stuart
Brain, Susan D.
author_sort Aubdool, Aisah A.
collection PubMed
description The cold-induced vascular response, consisting of vasoconstriction followed by vasodilatation, is critical for protecting the cutaneous tissues against cold injury. Whilst this physiological reflex response is historic knowledge, the mechanisms involved are unclear. Here by using a murine model of local environmental cold exposure, we show that TRPA1 acts as a primary vascular cold sensor, as determined through TRPA1 pharmacological antagonism or gene deletion. The initial cold-induced vasoconstriction is mediated via TRPA1-dependent superoxide production that stimulates α(2C)-adrenoceptors and Rho-kinase-mediated MLC phosphorylation, downstream of TRPA1 activation. The subsequent restorative blood flow component is also dependent on TRPA1 activation being mediated by sensory nerve-derived dilator neuropeptides CGRP and substance P, and also nNOS-derived NO. The results allow a new understanding of the importance of TRPA1 in cold exposure and provide impetus for further research into developing therapeutic agents aimed at the local protection of the skin in disease and adverse climates.
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spelling pubmed-42848112015-01-13 TRPA1 is essential for the vascular response to environmental cold exposure Aubdool, Aisah A. Graepel, Rabea Kodji, Xenia Alawi, Khadija M. Bodkin, Jennifer V. Srivastava, Salil Gentry, Clive Heads, Richard Grant, Andrew D. Fernandes, Elizabeth S. Bevan, Stuart Brain, Susan D. Nat Commun Article The cold-induced vascular response, consisting of vasoconstriction followed by vasodilatation, is critical for protecting the cutaneous tissues against cold injury. Whilst this physiological reflex response is historic knowledge, the mechanisms involved are unclear. Here by using a murine model of local environmental cold exposure, we show that TRPA1 acts as a primary vascular cold sensor, as determined through TRPA1 pharmacological antagonism or gene deletion. The initial cold-induced vasoconstriction is mediated via TRPA1-dependent superoxide production that stimulates α(2C)-adrenoceptors and Rho-kinase-mediated MLC phosphorylation, downstream of TRPA1 activation. The subsequent restorative blood flow component is also dependent on TRPA1 activation being mediated by sensory nerve-derived dilator neuropeptides CGRP and substance P, and also nNOS-derived NO. The results allow a new understanding of the importance of TRPA1 in cold exposure and provide impetus for further research into developing therapeutic agents aimed at the local protection of the skin in disease and adverse climates. Nature Pub. Group 2014-12-11 /pmc/articles/PMC4284811/ /pubmed/25501034 http://dx.doi.org/10.1038/ncomms6732 Text en Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Aubdool, Aisah A.
Graepel, Rabea
Kodji, Xenia
Alawi, Khadija M.
Bodkin, Jennifer V.
Srivastava, Salil
Gentry, Clive
Heads, Richard
Grant, Andrew D.
Fernandes, Elizabeth S.
Bevan, Stuart
Brain, Susan D.
TRPA1 is essential for the vascular response to environmental cold exposure
title TRPA1 is essential for the vascular response to environmental cold exposure
title_full TRPA1 is essential for the vascular response to environmental cold exposure
title_fullStr TRPA1 is essential for the vascular response to environmental cold exposure
title_full_unstemmed TRPA1 is essential for the vascular response to environmental cold exposure
title_short TRPA1 is essential for the vascular response to environmental cold exposure
title_sort trpa1 is essential for the vascular response to environmental cold exposure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284811/
https://www.ncbi.nlm.nih.gov/pubmed/25501034
http://dx.doi.org/10.1038/ncomms6732
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