Bitter taste receptor agonists regulate epithelial two-pore potassium channels via cAMP signaling.
Bitter taste receptor agonists regulate epithelial two-pore potassium channels via cAMP signaling.
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DOI：
10.1186/s12931-021-01631-0
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发表时间：
2021-01-28
影响因子：
5.8
通讯作者：
Cohen NA
中科院分区：
文献类型：
--
作者：
Kohanski MA;Brown L;Orr M;Tan LH;Adappa ND;Palmer JN;Rubenstein RC;Cohen NA
苦味信号转导主要通过G蛋白偶联受体和钙依赖性信号通路进行。利用相同苦味信号转导途径的II型味觉细胞也可以利用环磷酸腺苷（cAMP）作为除钙之外的独立信号传导信使。在这项工作中，我们利用特定的药理学抑制剂，询问短路电流（Isc）的极化鼻上皮细胞安装在Ussing室，以评估与苦味激动剂（地那铵）治疗相关的电生理变化。我们还评估了苯甲酸地那铵和/或钾通道抑制剂处理后极化鼻上皮培养物中人β-防御素-2的释放。我们证明，苦味受体激动剂，地那铵，降低人呼吸道上皮细胞的两孔钾（K2 P）电流极化鼻上皮细胞安装在尤辛室。我们的数据进一步表明，这是通过cAMP依赖性信号通路发生的。我们还证明，这种钾电流的减少降低了地那铵刺激人β-防御素-2释放的阈值。因此，这些数据表明，除了味觉转导钙依赖性信号传导外，苦味受体激动剂还可以激活cAMP依赖性呼吸上皮信号传导途径以调节K2 P电流。因此，苦味激动剂调节钾电流可能作为一种手段，快速区域上皮信号，这些途径的进一步研究可能提供新的见解调节粘膜离子组成和先天机制的上皮防御。
Epithelial solitary chemosensory cell (tuft cell) bitter taste signal transduction occurs through G protein coupled receptors and calcium-dependent signaling pathways. Type II taste cells, which utilize the same bitter taste signal transduction pathways, may also utilize cyclic adenosine monophosphate (cAMP) as an independent signaling messenger in addition to calcium. In this work we utilized specific pharmacologic inhibitors to interrogate the short circuit current (Isc) of polarized nasal epithelial cells mounted in Ussing chambers to assess the electrophysiologic changes associated with bitter agonist (denatonium) treatment. We also assessed release of human β-defensin-2 from polarized nasal epithelial cultures following treatment with denatonium benzoate and/or potassium channel inhibitors. We demonstrate that the bitter taste receptor agonist, denatonium, decreases human respiratory epithelial two-pore potassium (K2P) current in polarized nasal epithelial cells mounted in Ussing chambers. Our data further suggest that this occurs via a cAMP-dependent signaling pathway. We also demonstrate that this decrease in potassium current lowers the threshold for denatonium to stimulate human β-defensin-2 release. These data thus demonstrate that, in addition to taste transducing calcium-dependent signaling, bitter taste receptor agonists can also activate cAMP-dependent respiratory epithelial signaling pathways to modulate K2P currents. Bitter-agonist regulation of potassium currents may therefore serve as a means of rapid regional epithelial signaling, and further study of these pathways may provide new insights into regulation of mucosal ionic composition and innate mechanisms of epithelial defense.
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影响因子：
24.8
作者：
Bankova LG;Dwyer DF;Yoshimoto E;Ualiyeva S;McGinty JW;Raff H;von Moltke J;Kanaoka Y;Frank Austen K;Barrett NA
通讯作者：
Barrett NA
影响因子：
64.8
作者：
Gerbe F;Sidot E;Smyth DJ;Ohmoto M;Matsumoto I;Dardalhon V;Cesses P;Garnier L;Pouzolles M;Brulin B;Bruschi M;Harcus Y;Zimmermann VS;Taylor N;Maizels RM;Jay P
通讯作者：
Jay P
影响因子：
15.9
作者：
Lee, Robert J.;Xiong, Guoxiang;Cohen, Noam A.
通讯作者：
Cohen, Noam A.
DOI：
10.3410/b3-20
发表时间：
2011
期刊：
F1000 biology reports
影响因子：
--
作者：
Finger TE;Kinnamon SC
通讯作者：
Kinnamon SC
簇细胞，味觉化学细胞，在肠道中编排寄生虫2型免疫力。
DOI：
10.1126/science.aaf1648
发表时间：
2016-03-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Howitt MR;Lavoie S;Michaud M;Blum AM;Tran SV;Weinstock JV;Gallini CA;Redding K;Margolskee RF;Osborne LC;Artis D;Garrett WS
通讯作者：
Garrett WS