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

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

Journal

Nature Communications Nature Publishing Group: Nature Communications

Publisher: Nature Publishing Group: Nature Communications

Book Volume: 5

Article Number: 4381

DOI: 10.1038/ncomms5381

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 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.

Authors with CRIS profile

Barbara Namer Lehrstuhl für Physiologie Jan Miljkovic Lehrstuhl für Bioanorganische Chemie Tetyana Kichko Lehrstuhl für Physiologie Angelika Lampert Lehrstuhl für Physiologie Ivana Ivanovic-Burmazovic Lehrstuhl für Bioanorganische Chemie Karl Meßlinger Professur für Zelluläre und Molekulare Neurophysiologie Peter Reeh Professur für Physiologie Milos Filipovic Lehrstuhl für Bioanorganische Chemie

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE)

How to cite

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://dx.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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