{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:11:57Z","timestamp":1792213917264,"version":"4.4.0"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82570647"],"award-info":[{"award-number":["No. 82570647"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82273115"],"award-info":[{"award-number":["No. 82273115"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Although acetylcholine (ACh) released by the vagus nerve can stimulate enterochromaffin cells (ECs) to secrete 5-hydroxytryptamine (5-HT), the precise regulatory mechanism underlying this process and its association with the pathogenesis of ulcerative colitis (UC) remain unclear. In this study, we aimed to investigate whether TRPV4-mediated calcium influx in ECs is involved the process of ACh promoting 5-HT secretion which leads to UC. In vitro experiments, western blotting, cellular calcium imaging, and patch clamp were applied to ECs, and dextran sulfate sodium (DSS)-induced UC of mouse model was used in vivo. Carbachol (CCh), a stable analog of ACh, activated mAChR\/IP\n                    <jats:sub>3<\/jats:sub>\n                    \/IP\n                    <jats:sub>3<\/jats:sub>\n                    R pathway to increase intracellular [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    levels in ECs, in which both TRPV4 channels and RyR were activated in response to CCh. The selective TRPV4 antagonist HC067047 inhibited the calcium signals and membrane currents induced by IP3\/IP3R, as well as 5-HT secretion. In addition, selective blocker of RyR (Dantrolene) also significantly inhibited CCh-induced calcium signals and membrane currents. In vivo experiments, HC067047 significantly suppressed the synthesis and release of 5-HT from ECs and alleviated DSS-induced UC in mice. Taken together, this study reveals a novel mAChR\/IP\n                    <jats:sub>3<\/jats:sub>\n                    \/IP\n                    <jats:sub>3<\/jats:sub>\n                    R \/TRPV4\/5-HT pathway in ECs is likely involved in the pathogenesis of UC. Targeting this pathway holds a promise for the potential prevention and treatment of UC.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0355169","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T17:27:05Z","timestamp":1786642025000},"page":"e0355169","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular regulatory mechanism of TRPV4-mediated calcium-dependent 5-HT secretion from enterochromaffin cells and its involvement in ulcerative colitis"],"prefix":"10.1371","volume":"21","author":[{"given":"Shuo","family":"Tong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxin","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shude","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2587-8360","authenticated-orcid":true,"given":"Hui","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"pone.0355169.ref001","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1146\/annurev-physiol-021115-105439","article-title":"Enteroendocrine 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(Lausanne)"},{"issue":"13","key":"pone.0355169.ref031","doi-asserted-by":"crossref","first-page":"3924","DOI":"10.1021\/acs.jafc.9b08163","article-title":"Structure-Dependent Effects of Cinnamaldehyde Derivatives on TRPA1-Induced Serotonin Release in Human Intestinal Cell Models","volume":"68","author":"B Lieder","year":"2020","journal-title":"J Agric Food Chem"},{"issue":"3","key":"pone.0355169.ref032","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1530\/JME-16-0063","article-title":"Helional induces Ca2+ decrease and serotonin secretion of QGP-1 cells via a PKG-mediated pathway","volume":"57","author":"B Kalbe","year":"2016","journal-title":"J Mol Endocrinol"},{"key":"pone.0355169.ref033","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1111\/bph.15193","article-title":"The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research","volume":"177","author":"N Percie du Sert","year":"2020","journal-title":"Br J Pharmacol"},{"key":"pone.0355169.ref034","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1177\/1747493018778713","article-title":"Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke","volume":"13","author":"From the American Association of Neurological Surgeons (AANS), American Society of Neuroradiology (ASNR), Cardiovascular and Interventional Radiology Society of Europe (CIRSE), Canadian Interventional Radiology Association (CIRA), Congress of Neurological Surgeons (CNS), European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), European Stroke Organization (ESO), Society for Cardiovascular Angiography and Interventions (SCAI), Society of Interventional Radiology (SIR), Society of NeuroInterventional Surgery (SNIS), and World Stroke Organization (WSO)","year":"2018","journal-title":"Int J Stroke"},{"issue":"4","key":"pone.0355169.ref035","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"KJ Livak","year":"2001","journal-title":"Methods"},{"key":"pone.0355169.ref036","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/1471-2105-13-134","article-title":"Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction","volume":"13","author":"J Ye","year":"2012","journal-title":"BMC Bioinformatics"},{"key":"pone.0355169.ref037","doi-asserted-by":"crossref","first-page":"115828","DOI":"10.1016\/j.bcp.2023.115828","article-title":"Zinc pyrithione induces endothelium-dependent hyperpolarization-mediated mesenteric vasorelaxation in healthy and colitic mice","volume":"217","author":"C Sun","year":"2023","journal-title":"Biochem Pharmacol"},{"key":"pone.0355169.ref038","doi-asserted-by":"crossref","first-page":"327","DOI":"10.3390\/ijms22010327","article-title":"Neurotransmitter Release Site Replenishment and Presynaptic Plasticity","volume":"22","author":"S Mochida","year":"2020","journal-title":"Int J Mol Sci"},{"key":"pone.0355169.ref039","doi-asserted-by":"crossref","first-page":"684538","DOI":"10.3389\/fphar.2021.684538","article-title":"Role of Serosal TRPV4-Constituted SOCE Mechanism in Secretagogues-Stimulated Intestinal Epithelial Anion Secretion","volume":"12","author":"Y Cui","year":"2021","journal-title":"Front Pharmacol"},{"key":"pone.0355169.ref040","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/bs.ircmb.2020.02.003","article-title":"Type 3 IP3 receptors: The chameleon in cancer","volume":"351","author":"N Rosa","year":"2020","journal-title":"Int Rev Cell Mol Biol"},{"issue":"6","key":"pone.0355169.ref041","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1111\/j.1476-5381.2010.01152.x","article-title":"Inhibition of inositol monophosphatase by lithium chloride induces selective macrophage apoptosis in atherosclerotic plaques","volume":"162","author":"I De Meyer","year":"2011","journal-title":"Br J Pharmacol"},{"key":"pone.0355169.ref042","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1113\/jphysiol.1992.sp019015","article-title":"The inositol 1,4,5-trisphosphate pathway mediates cholinergic potentiation of rat hippocampal neuronal responses to NMDA","volume":"447","author":"H Markram","year":"1992","journal-title":"J Physiol"},{"issue":"3","key":"pone.0355169.ref043","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/S0896-6273(00)80384-0","article-title":"Xestospongins: potent membrane permeable blockers of the inositol 1,4,5-trisphosphate receptor","volume":"19","author":"J Gafni","year":"1997","journal-title":"Neuron"},{"issue":"24","key":"pone.0355169.ref044","doi-asserted-by":"crossref","first-page":"6827","DOI":"10.1113\/JP287092","article-title":"TRPV4 couples with NCX1 to mediate glucose-dependent glucagon-like peptide-1 release and improve glucose homeostasis","volume":"602","author":"X Chen","year":"2024","journal-title":"J Physiol"},{"issue":"1","key":"pone.0355169.ref045","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s10020-022-00448-x","article-title":"Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways","volume":"28","author":"Z Cheng","year":"2022","journal-title":"Mol Med"},{"issue":"2","key":"pone.0355169.ref046","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/bph.15287","article-title":"Small intestinal glucose and sodium absorption through calcium-induced calcium release and store-operated Ca2+ entry mechanisms","volume":"178","author":"F Zhang","year":"2021","journal-title":"Br J Pharmacol"},{"issue":"9","key":"pone.0355169.ref047","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1038\/s41423-021-00725-5","article-title":"Mobilizing ER IP3 receptors as a mechanism to enhance calcium signaling","volume":"18","author":"L Lu","year":"2021","journal-title":"Cell Mol Immunol"},{"issue":"4","key":"pone.0355169.ref048","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.ceca.2011.06.002","article-title":"Ouabain enhances exocytosis through the regulation of calcium handling by the endoplasmic reticulum of chromaffin cells","volume":"50","author":"J Milla","year":"2011","journal-title":"Cell Calcium"},{"issue":"4","key":"pone.0355169.ref049","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.matbio.2010.02.002","article-title":"Glycosaminoglycan mimetics trigger IP3-dependent intracellular calcium release in myoblasts","volume":"29","author":"I Martelly","year":"2010","journal-title":"Matrix Biol"},{"issue":"51","key":"pone.0355169.ref050","doi-asserted-by":"crossref","first-page":"30530","DOI":"10.1074\/jbc.M115.682583","article-title":"Store-operated Ca2+ Entry Mediated by Orai1 and TRPC1 Participates to Insulin Secretion in Rat \u03b2-Cells","volume":"290","author":"J Sabourin","year":"2015","journal-title":"J Biol Chem"},{"issue":"6","key":"pone.0355169.ref051","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3390\/cells7060061","article-title":"Expression Profiling of the Transient Receptor Potential Vanilloid (TRPV) Channels 1, 2, 3 and 4 in Mucosal Epithelium of Human Ulcerative Colitis","volume":"7","author":"T Rizopoulos","year":"2018","journal-title":"Cells"},{"issue":"1","key":"pone.0355169.ref052","doi-asserted-by":"crossref","DOI":"10.1152\/ajpgi.00105.2013","article-title":"Role of transient receptor potential vanilloid 4 activation in indomethacin-induced intestinal damage","volume":"307","author":"H Yamawaki","year":"2014","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"pone.0355169.ref053","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ejphar.2015.02.042","article-title":"L-type calcium channels contribute to 5-HT3-receptor-evoked CaMKII\u03b1 and ERK activation and induction of emesis in the least shrew (Cryptotis parva)","volume":"755","author":"TE Hutchinson","year":"2015","journal-title":"Eur J Pharmacol"},{"issue":"4","key":"pone.0355169.ref054","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1152\/physrev.00040.2008","article-title":"Calcium-induced calcium release in skeletal muscle","volume":"89","author":"M Endo","year":"2009","journal-title":"Physiol Rev"}],"container-title":["PLOS 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