Eberhard M, Dux M, Namer B, Miljkovic J, Cordasic N, Will C, Kichko T, de la Roche J, Fischer MJM, Suarez SA, Bikiel D, Dorsch K, Leffler A, Babes A, Lampert A, Lennerz JK, Jacobi J, Marti MA, Doctorovich F, Högestätt ED, Zygmunt PM, Ivanovic-Burmazovic I, Meßlinger K, Reeh P, Filipovic M (2014)
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2014
Publisher: Nature Publishing Group: Nature Communications
Book Volume: 5
Article Number: 4381
DOI: 10.1038/ncomms5381
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 H 2 S. We show that H 2 S 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. H 2 S-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. © 2014 Macmillan Publishers Limited. All rights reserved.
APA:
Eberhard, M., Dux, M., Namer, B., Miljkovic, J., Cordasic, N., Will, C.,... Filipovic, M. (2014). H2S and NO cooperatively regulate vascular tone by activating a neuroendocrine HNO-TRPA1-CGRP signalling pathway. Nature Communications, 5. https://doi.org/10.1038/ncomms5381
MLA:
Eberhard, Miriam, et al. "H2S and NO cooperatively regulate vascular tone by activating a neuroendocrine HNO-TRPA1-CGRP signalling pathway." Nature Communications 5 (2014).
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