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

作者：Yinghui Cui, Fenglan Chu, Kai Yin, Xiongying Chen, Hanxing Wan, Gang Luo, Hui Dong, Feng Xu · 发表于：Frontiers in Pharmacology · 年份：2021 · DOI：10.3389/fphar.2021.684538 · 被引用次数：15 · 研究领域：Ion Channels and Receptors、Gastrointestinal motility and disorders、Helicobacter pylori-related gastroenterology studies

As little is known about the role of calcium (Ca 2+ ) 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 μM) and 5-HT (10 μM) induced mouse duodenal I sc , markedly attenuated by serosal Ca 2+ -free solution and selective blockers of store-operated Ca 2+ channels on the serosal side of the duodenum. Furthermore, PGE 2 - and 5-HT-induced duodenal I sc was also inhibited by ER Ca 2+ chelator TPEN. However, dantrolene, a selective blocker of ryanodine receptors, inhibited PGE 2 -induced duodenal I sc , while LiCl, an inhibitor of IP 3 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 μM) also induced duodenal I sc via selective activation of muscarinic receptors, which was significantly inhibited in serosal Ca 2+ -free solution but neither in mucosal Ca 2+ -free solution nor by nifedipine. Therefore, the serosal TRPV4-constituted SOCE mechanism is likely universal for the most common and important secretagogues-induced and Ca ...