Role of Serosal TRPV4-Constituted SOCE Mechanism in Secretagogues-Stimulated Intestinal Epithelial Anion Secretion

作者全名："Cui, Yinghui; Chu, Fenglan; Yin, Kai; Chen, Xiongying; Wan, Hanxing; Luo, Gang; Dong, Hui; Xu, Feng"

作者地址："[Cui, Yinghui; Chen, Xiongying; Wan, Hanxing; Dong, Hui; Xu, Feng] Chongqing Med Univ, Dept Pediat Intens Care Unit, Childrens Hosp, Chongqing, Peoples R China; [Cui, Yinghui; Chen, Xiongying; Wan, Hanxing; Dong, Hui; Xu, Feng] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China; [Cui, Yinghui; Chen, Xiongying; Wan, Hanxing; Dong, Hui; Xu, Feng] Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China; [Cui, Yinghui; Chen, Xiongying; Wan, Hanxing; Dong, Hui; Xu, Feng] Chongqing Key Lab Pediat, Chongqing, Peoples R China; [Chu, Fenglan; Yin, Kai; Luo, Gang; Dong, Hui] Army Med Univ, Xinqiao Hosp, Dept Gastroenterol, Chongqing, Peoples R China"

通信作者："Dong, H; Xu, F (corresponding author), Chongqing Med Univ, Dept Pediat Intens Care Unit, Childrens Hosp, Chongqing, Peoples R China.; Dong, H; Xu, F (corresponding author), Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China.; Dong, H; Xu, F (corresponding author), Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China.; Dong, H; Xu, F (corresponding author), Chongqing Key Lab Pediat, Chongqing, Peoples R China.; Dong, H (corresponding author), Army Med Univ, Xinqiao Hosp, Dept Gastroenterol, Chongqing, Peoples R China."

来源：FRONTIERS IN PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000680732100001

JCR分区：Q1

影响因子：5.6

年份：2021

卷号：12

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：calcium signaling; PGE(2); 5-HT; SOCE; CRAC; TRPV4; CCH

摘要："As little is known about the role of calcium (Ca2+) signaling mediating the small intestinal epithelial anion secretion, we aimed to study its regulatory role in secretagogue-stimulated duodenal anion secretion and the underlying molecular mechanisms. Therefore, intestinal anion secretion from native mouse duodenal epithelia was examined with Ussing chambers to monitor PGE(2)-, 5-HT-, and CCh-induced short-circuit currents (I-sc). PGE(2) (10 mu M) and 5-HT (10 mu M) induced mouse duodenal I-sc, markedly attenuated by serosal Ca2+-free solution and selective blockers of store-operated Ca2+ channels on the serosal side of the duodenum. Furthermore, PGE(2)- and 5-HT-induced duodenal I-sc was also inhibited by ER Ca2+ chelator TPEN. However, dantrolene, a selective blocker of ryanodine receptors, inhibited PGE(2)-induced duodenal I-sc , while LiCl, an inhibitor of IP3 production, inhibited 5-HT-induced I-sc. Moreover, duodenal I-sc response to the serosal applications of both PGE(2) and 5-HT was significantly attenuated in transient receptor potential vanilloid 4 (TRPV4) knockout mice. Finally, mucosal application of carbachol (100 mu M) also induced duodenal I-sc via selective activation of muscarinic receptors, which was significantly inhibited in serosal Ca2+-free solution but neither in mucosal Ca2+-free solution nor by nifedipine. Therefore, the serosal TRPV4-constituted SOCE mechanism is likely universal for the most common and important secretagogues-induced and Ca2+-dependent intestinal anion secretion. These findings will enhance our knowledge about gastrointestinal (G.I.) epithelial physiology and the associated G.I. diseases, such as diarrhea and constipation."

基金机构："China's National Key Research and Development Program [2016YFC1302200]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81873544, 81602474]"

基金资助正文："This study was supported by research grants from China's National Key Research and Development Program (No. 2016YFC1302200 to H.D.) and the National Natural Science Foundation of China (No. 81873544 to H.D., and No. 81602474 to G.L.)."