title: Polysulfides (H2Sn) produced from the interaction of hydrogen sulfide (H2S) and nitric oxide (NO) activate TRPA1 channels.
abstract: Hydrogen sulfide (H2S) exerts synergistic effects with another gaseous signaling molecule nitric oxide (NO) on ion channels and vasculature. However, the mechanism of the synergy is not well understood. Here, we show that the interaction between H2S and NO generates polysulfides (H2Sn), which activate transient receptor potential ankyrin 1 (TRPA1) channels. High performance liquid chromatography with tandem mass spectrometry analysis, along with the imaging of intracellular Ca2+and H2Sn, showed that H2Snand their effects were abolished by cyanolysis and by reducing substances such as dithiothreitol (DTT), cysteine, and glutathione (GSH). However, the effects of nitroxyl or nitrosopersulfide, other potential products of H2S and NO interaction, are not affected by cyanolysis or reducing substances. This study demonstrates that H2Snare products of synergy between H2S and NO and provides a new insight into the signaling mechanisms.
authors.affiliation: Department of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Miyamoto
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-552-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Koike
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takano
authors.affiliation: Department of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Shibuya
authors.affiliation: Department of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Hanaoka
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Urano
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-552-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ogasawara
authors.affiliation: Department of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Kimura
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000494:pharmacology*; D000074025:TRPA1 Cation Channel / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D013440:Sulfides; D000074025:TRPA1 Cation Channel; D009569:Nitric Oxide; C032915:polysulfide; D002118:Calcium; D006862:Hydrogen Sulfide