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H2S and NO cooperatively regulate vascular tone by activating a neuroendocrine HNO-TRPA1-CGRP signalling pathway.

Eberhardt, Mirjam; Dux, Maria; Namer, Barbara; Miljkovic, Jan; Cordasic, Nada; Will, Christine; Kichko, Tatjana I; de la Roche, Jeanne; Fischer, Michael and Suárez, Sebastián A, et al. (2014) In Nature Communications 5(Jul 15).
Abstract
Nitroxyl (HNO) is a redox sibling of nitric oxide (NO) that targets distinct signalling pathways with pharmacological endpoints of high significance in the treatment of heart failure. Beneficial HNO effects depend, in part, on its ability to release calcitonin gene-related peptide (CGRP) through an unidentified mechanism. Here we propose that HNO is generated as a result of the reaction of the two gasotransmitters NO and H2S. We show that H2S and NO production colocalizes with transient receptor potential channel A1 (TRPA1), and that HNO activates the sensory chemoreceptor channel TRPA1 via formation of amino-terminal disulphide bonds, which results in sustained calcium influx. As a consequence, CGRP is released, which induces local and... (More)
Nitroxyl (HNO) is a redox sibling of nitric oxide (NO) that targets distinct signalling pathways with pharmacological endpoints of high significance in the treatment of heart failure. Beneficial HNO effects depend, in part, on its ability to release calcitonin gene-related peptide (CGRP) through an unidentified mechanism. Here we propose that HNO is generated as a result of the reaction of the two gasotransmitters NO and H2S. We show that H2S and NO production colocalizes with transient receptor potential channel A1 (TRPA1), and that HNO activates the sensory chemoreceptor channel TRPA1 via formation of amino-terminal disulphide bonds, which results in sustained calcium influx. As a consequence, CGRP is released, which induces local and systemic vasodilation. H2S-evoked vasodilatatory effects largely depend on NO production and activation of HNO-TRPA1-CGRP pathway. We propose that this neuroendocrine HNO-TRPA1-CGRP signalling pathway constitutes an essential element for the control of vascular tone throughout the cardiovascular system. (Less)
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Nature Communications
volume
5
issue
Jul 15
publisher
Nature Publishing Group
external identifiers
  • pmid:25023795
  • wos:000340617600001
  • scopus:84904490728
ISSN
2041-1723
DOI
10.1038/ncomms5381
language
English
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yes
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858c3aba-e288-4706-bddb-88d635fbbe9a (old id 4582307)
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http://www.ncbi.nlm.nih.gov/pubmed/25023795?dopt=Abstract
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2014-08-07 23:55:49
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2017-11-19 03:43:42
@article{858c3aba-e288-4706-bddb-88d635fbbe9a,
  abstract     = {Nitroxyl (HNO) is a redox sibling of nitric oxide (NO) that targets distinct signalling pathways with pharmacological endpoints of high significance in the treatment of heart failure. Beneficial HNO effects depend, in part, on its ability to release calcitonin gene-related peptide (CGRP) through an unidentified mechanism. Here we propose that HNO is generated as a result of the reaction of the two gasotransmitters NO and H2S. We show that H2S and NO production colocalizes with transient receptor potential channel A1 (TRPA1), and that HNO activates the sensory chemoreceptor channel TRPA1 via formation of amino-terminal disulphide bonds, which results in sustained calcium influx. As a consequence, CGRP is released, which induces local and systemic vasodilation. H2S-evoked vasodilatatory effects largely depend on NO production and activation of HNO-TRPA1-CGRP pathway. We propose that this neuroendocrine HNO-TRPA1-CGRP signalling pathway constitutes an essential element for the control of vascular tone throughout the cardiovascular system.},
  articleno    = {4381},
  author       = {Eberhardt, Mirjam and Dux, Maria and Namer, Barbara and Miljkovic, Jan and Cordasic, Nada and Will, Christine and Kichko, Tatjana I and de la Roche, Jeanne and Fischer, Michael and Suárez, Sebastián A and Bikiel, Damian and Dorsch, Karola and Leffler, Andreas and Babes, Alexandru and Lampert, Angelika and Lennerz, Jochen K and Jacobi, Johannes and Martí, Marcelo A and Doctorovich, Fabio and Högestätt, Edward and Zygmunt, Peter and Ivanovic-Burmazovic, Ivana and Messlinger, Karl and Reeh, Peter and Filipovic, Milos R},
  issn         = {2041-1723},
  language     = {eng},
  number       = {Jul 15},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {H2S and NO cooperatively regulate vascular tone by activating a neuroendocrine HNO-TRPA1-CGRP signalling pathway.},
  url          = {http://dx.doi.org/10.1038/ncomms5381},
  volume       = {5},
  year         = {2014},
}