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Here we found mucosal application of MSG induced an upward intestinal short\u2010circuit current (\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>sc<\/jats:italic>\n                    <\/jats:sub>\n                    ) in the murine ileum, which was significantly reduced by extracellular Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    , Na\n                    <jats:sup>+<\/jats:sup>\n                    , and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    removal. Mechanistically, MSG\u2010induced\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>sc<\/jats:italic>\n                    <\/jats:sub>\n                    was significantly attenuated by pharmacological inhibition of key transporters (NCX, SGLT1, NKA) and secretory channels (CaCC, CFTR, IK\n                    <jats:sub>Ca<\/jats:sub>\n                    ). Furthermore, disrupting intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis via endoplasmic reticulum (ER) chelation or blockade of IP\n                    <jats:sub>3<\/jats:sub>\n                    R, RyR, SOCE\/CRAC, and VGCC significantly suppressed both the ileal\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>sc<\/jats:italic>\n                    <\/jats:sub>\n                    and MSG\u2010stimulated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling in IECs. Importantly, MSG triggered a simultaneous elevation in intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and a reduction in Na\n                    <jats:sup>+<\/jats:sup>\n                    , which were abolished by the blockers of NCX and SGLT1. In\u00a0vivo, MSG\u2010induced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent ion transports were significantly reduced in irritable bowel syndrome with diarrhea (IBS\u2010D) mice. Our findings indicate that MSG drives Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent intestinal ion transports through a complex network orchestrated by SGLT1 and NCX under healthy state, which is markedly attenuated in IBS\u2010D. This study provides novel insights into the gastrointestinal impact of dietary MSG in both health and bowel disease.\n                  <\/jats:p>","DOI":"10.14814\/phy2.70975","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T07:22:33Z","timestamp":1781248953000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Monosodium glutamate\u2010mediated Ca\n                    <sup>2+<\/sup>\n                    \u2010dependent intestinal epithelial ion transports in health and\n                    <scp>IBS<\/scp>\n                    \u2010D in male mice"],"prefix":"10.14814","volume":"14","author":[{"given":"Yunxian","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Pharmacy, Qingdao University Medical College  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenglan","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy, Qingdao University Medical College  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy, Qingdao University Medical College  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy, Qingdao University Medical College  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2587-8360","authenticated-orcid":false,"given":"Hui","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy, Qingdao University Medical College  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2018.08.006"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13051506"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2001.280.5.G922"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.05.028"},{"key":"e_1_2_12_6_1","first-page":"49","volume-title":"Methods in molecular biology","author":"Bahadoran Z.","year":"2019"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2019.07.005"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0149\u20107634(98)00043\u20108"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14596"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2009.27462Y"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00186.2019"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/15376516.2018.1528649"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07\u2010099697"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.816133"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.684538"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017\u201000258"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/1750\u20103841.16101"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00381.2004"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.14"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000000346"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2409049121"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiologyonline.2001.16.1.23"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440\u20101746.2011.06631.x"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.62.14.25"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00030"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293\u2010024\u201000633\u2010z"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2024.1352832"},{"key":"e_1_2_12_28_1","first-page":"10","article-title":"The effect of dietary glutamate on fibromyalgia and irritable bowel symptoms","volume":"30","author":"Holton K. 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