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

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 nat...

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Detalles Bibliográficos
Autores principales: Cui, Yinghui, Chu, Fenglan, Yin, Kai, Chen, Xiongying, Wan, Hanxing, Luo, Gang, Dong, Hui, Xu, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317263/
https://www.ncbi.nlm.nih.gov/pubmed/34335254
http://dx.doi.org/10.3389/fphar.2021.684538
Descripción
Sumario: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(2+)-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.