title: Polysulfides are possible H2S-derived signaling molecules in rat brain.
abstract: Accumulating evidence shows that hydrogen sulfide (H2S) has a variety of physiological functions. H2S is produced from cysteine by 3 sulfurtransferases. H2S, in turn, generates polysulfides, the functions of which are not well understood. H2S induces Ca(2+) influx in astrocytes, a type of glia. However, the receptor that mediates the response has not been identified. Here, we have shown that polysulfides induce Ca(2+) influx by activating transient receptor potential (TRP)A1 channels in rat astrocytes (EC50 91 nM, Hill coefficient value 1.77±0.26) and that the maximum response was induced at 0.5 μM, which is 1/320 of the concentration of H2S required to achieve a response of similar magnitude (160 μM, EC50 116 μM). TRPA1-selective agonists, allyl isothiocyanate and cinnamaldehyde, induced Ca(2+) influx, and responses to polysulfides were suppressed by TRPA1-selective inhibitors, HC-030031 and AP-18, as well as by siRNAs selective to TRPA1. The present study suggests that polysulfides are possible H2S-derived signaling molecules that stimulate TRP channels in the brain.
authors: Department of Molecular Pharmacology, National Institute of Neuroscience, Tokyo, Japan.
authors: Yuka
authors: Y
authors: Kimura
authors: Yoshinori
authors: Y
authors: Mikami
authors: Kimiko
authors: K
authors: Osumi
authors: Mamiko
authors: M
authors: Tsugane
authors: Jun-ichiro
authors: J
authors: Oka
authors: Hideo
authors: H
authors: Kimura
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D005682:Gadolinium / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D017879:Isothiocyanates / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D051379:Mice; D011687:Purines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012430:Ruthenium Red / Q000494:pharmacology; D015398:Signal Transduction; D013440:Sulfides / Q000378:metabolism*; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D017879:Isothiocyanates; D011687:Purines; D034741:RNA, Small Interfering; D013440:Sulfides; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D012430:Ruthenium Red; D007811:Lanthanum; D000171:Acrolein; C032915:polysulfide; D005682:Gadolinium; C004471:allyl isothiocyanate; C012843:cinnamaldehyde; D006862:Hydrogen Sulfide
keywords: Ca2+ influx; TRP channels; hydrogen sulfide; persulfide