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While CPZ is known to induce hyposalivation, the exact mechanism by which it inhibits secretory function in the salivary glands remains unclear. In this study, we investigated the molecular mechanism underlying CPZ-induced hyposalivation. Our findings confirmed that CPZ decreases salivation by inhibiting muscarinic signaling in a dose-dependent manner in a mouse model. By analyzing a single-cell RNA sequencing (scRNA-seq) database, we searched known CPZ targets in salivary gland cells and found that dopamine receptors are not expressed in these cells. CPZ inhibited the increase in intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    triggered by muscarinic and histamine receptors in human salivary gland cells. This inhibition involved both the release of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    from the endoplasmic reticulum (ER) and the influx of extracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    through store-operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry (SOCE). These findings suggest that in salivary glands, CPZ induces hyposalivation by inhibiting Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling through multiple sites of action, including muscarinic receptor and SOCE.\n                  <\/jats:p>","DOI":"10.1007\/s00210-025-04438-8","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T06:46:45Z","timestamp":1753253205000},"page":"941-951","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chlorpromazine induces hyposalivation by inhibiting muscarinic Ca2+ signaling in salivary glands"],"prefix":"10.1007","volume":"399","author":[{"given":"Yoon-Jung","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoo-Bin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soohyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae-Yong","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee-Kyung","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Se-Young","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"4438_CR1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1741-7015-3-15","volume":"3","author":"CE Adams","year":"2005","unstructured":"Adams CE, Rathbone J, Thornley B, Clarke M, Borrill J, Wahlbeck K, Awad AG (2005) Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials. 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