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Cibacron blue 3G-A is a novel inhibitor of Otopetrin 1 (OTOP1), a proton channel
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| Title: | Cibacron blue 3G-A is a novel inhibitor of Otopetrin 1 (OTOP1), a proton channel |
| Authors: | Islam, MD Mominul Browse this author | | Sasaki, Omi Browse this author | | Yano-Nashimoto, Saori Browse this author | | Okamatsu-Ogura, Yuko Browse this author →KAKEN DB | | Yamaguchi, Soichiro Browse this author →KAKEN DB |
| Keywords: | Otopetrin1 | | OTOP1 | | Proton channel | | Reactive blue 2 | | Cibacron blue 3G-A |
| Issue Date: | 29-Apr-2023 |
| Publisher: | Elsevier |
| Journal Title: | Biochemical and biophysical research communications |
| Volume: | 665 |
| Start Page: | 64 |
| End Page: | 70 |
| Publisher DOI: | 10.1016/j.bbrc.2023.04.112 |
| Abstract: | Otopetrin 1 (OTOP1) is a proton (H+) channel which detects acidic stimuli in sour taste receptor cells and plays some sort of role in the formation of otoconia in the inner ear. Although it is known that zinc ion (Zn2+) inhibits OTOP1, Zn2+ requires high concentrations (mM order) to inhibit OTOP1 sufficiently, and no other inhibitors have been found. Therefore, to identify a novel inhibitor, we screened a chemical library (LOPAC1280) by whole-cell patch clamp recordings, measuring proton currents of heterologously-expressed mouse OTOP1. From the screening, we found that reactive blue 2 inhibited OTOP1 currents. Further evaluations of three analogues of reactive blue 2 revealed that cibacron blue 3G-A potently inhibited OTOP1 currents. Cibacron blue 3G-A inhibited OTOP1 currents in a concentration-dependent manner, and its 50% inhibitory concentration (IC50) and the Hill coefficient were 5.0 mM and 1.1, respectively. The inhibition of OTOP1 currents by cibacron blue 3G-A was less affected by extracellular anion compositions, membrane potentials, and low pH than the inhibition by Zn2+. These results suggest that the inhibition of OTOP1 by cibacron blue 3G-A is neither likely to be a pore-blocking inhibition nor a competitive inhibition. Furthermore, our findings revealed that cibacron blue 3G-A can be used as a novel inhibitor of OTOP1 especially under the conditions in which OTOP1 activity is evaluated such as low pH. (c) 2023 Elsevier Inc. All rights reserved. |
| Rights: | © 2023. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/92064 |
| Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 山口 聡一郎
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