title: Bidirectional effects of hydrogen sulfide via ATP-sensitive K(+) channels and transient receptor potential A1 channels in RIN14B cells.
abstract: Hydrogen sulfide (H2S) reportedly acts as a gasotransmitter because it mediates various cellular responses through several ion channels including ATP-sensitive K(+) (KATP) channels and transient receptor potential (TRP) A1 channels. H2S can activate both KATP and TRPA1 channels at a similar concentration range. In a single cell expressing both channels, however, it remains unknown what happens when both channels are simultaneously activated by H2S. In this study, we examined the effects of H2S on RIN14B cells that express both KATP and TRPA1 channels. RIN14B cells showed several intracellular Ca(2+) concentration ([Ca(2+)]i) responses to NaHS (300 µM), an H2S donor, i.e., inhibition of spontaneous Ca(2+) oscillations (37%), inhibition followed by [Ca(2+)]i increase (24%), and a rapid increase in [Ca(2+)]i (25%). KATP channel blockers, glibenclamide or tolbutamide, abolished any inhibitory effects of NaHS and enhanced NaHS-mediated [Ca(2+)]i increases, which were inhibited by extracellular Ca(2+) removal, HC030031 (a TRPA1 antagonist), and disulfide bond-reducing agents. NaHS induced 5-hydroxytryptamine (5-HT) release from RIN14B cells, which was also inhibited by TRPA1 antagonists. These results indicate that H2S has both inhibitory and excitatory effects by opening KATP and TRPA1 channels, respectively, in RIN14B cells, suggesting potential bidirectional modulation of secretory functions.
authors.affiliation: Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Ujike
authors.affiliation: Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. Electronic address: otsuguro@vetmed.hokudai.ac.jp.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Otsuguro
authors.affiliation: Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Miyamoto
authors.affiliation: Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ito
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D054086:KATP Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D019864:Somatostatin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology*; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D054086:KATP Channels; D013440:Sulfides; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D012701:Serotonin; C025451:sodium bisulfide; D006862:Hydrogen Sulfide
keywords: Ca(2+) signal; Hydrogen sulfide; K(ATP) channels; RIN14B cells; TRPA1