2024-03-29T12:26:49Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/629582022-11-17T02:08:08Zhdl_2115_20048hdl_2115_140Bidirectional effects of hydrogen sulfide via ATP-sensitive K+ channels and transient receptor potential A1 channels in RIN14B cellsUjike, Ayako1000040344494Otsuguro, Ken-ichiMiyamoto, Ryo1000050596864Yamaguchi, Soichiro1000040109509Ito, Shigeoopen access©2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 InternationalHydrogen sulfideCa2+ signalTRPA1K-ATP channelsRIN14B cells491Hydrogen sulfide (H2S) reportedly acts as a gasotransmitter because it mediates various cellular responses through several ion channels including ATP-sensitive K+ (K-ATP) channels and transient receptor potential (TRP) A1 channels. H2S can activate both K-ATP, 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 K-ATP and TRPA1 channels. RIN14B cells showed several intracellular Ca2+ concentration ([Ca2+](i)) responses to NaHS (300 mu M), an H2S donor, i.e., inhibition of spontaneous Ca2+ oscillations (37%), inhibition followed by [Ca2+](i) increase (24%), and a rapid increase in [Ca2+](i) (25%). K-ATP channel blockers, glibenclamide or tolbutamide, abolished any inhibitory effects of NaHS and enhanced NaHS-mediated [Ca2+](i) increases, which were inhibited by extracellular Ca2+ 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 K-ATP and TRPA1 channels, respectively, in RIN14B cells, suggesting potential bidirectional modulation of secretory functions. (C) 2015 Elsevier B.V. All rights reserved.Elsevier2015-10-05engjournal articleAMhttp://hdl.handle.net/2115/62958https://doi.org/10.1016/j.ejphar.2015.07.029261720810014-29991879-0712AA00639687European Journal of Pharmacology764463470https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/62958/1/Eur.J.Pharmacol.764p463-470.pdfapplication/pdf508.0 KB2015-10-05