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Zn<jats:sup>2+<\/jats:sup> can evoke G-protein-coupled receptor signaling via activation of the metabotropic zinc receptor ZnR\/GPR39. In spite of evidence suggesting the presence of ZnR\/GPR39 in salivary gland cells, there has been no evidence of ZnR\/GPR39-mediated modulation of salivary gland function. Here we characterized the role of ZnR\/GPR39 in human submandibular gland cells. A 0.25% ZnCl<jats:sub>2<\/jats:sub> solution evoked secretion of unstimulated and stimulated whole saliva in humans. We found that ZnR\/GPR39 is expressed in human submandibular glands and HSG cells. Zn<jats:sup>2+<\/jats:sup> increased cytosolic Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) in a concentration-dependent manner. Muscarinic antagonist had no effect on Zn<jats:sup>2+<\/jats:sup>-induced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> increase, which was completely blocked by the phospholipase C-\u03b2 inhibitor. As with muscarinic agonist, Zn<jats:sup>2+<\/jats:sup> also induced the translocation of aquaporin-5 (AQP-5) to the plasma membrane, which was drastically decreased in ZnR\/GPR39-knockdown cells. These data suggest that the metabotropic Zn<jats:sup>2+<\/jats:sup> receptor ZnR\/GPR39 can modulate salivary secretion in human submandibular gland cells independent of muscarinic or histamine receptor signaling.<\/jats:p>","DOI":"10.1038\/s41598-019-54173-3","type":"journal-article","created":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T11:02:46Z","timestamp":1574852566000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Zn2+ stimulates salivary secretions via metabotropic zinc receptor ZnR\/GPR39 in human salivary gland cells"],"prefix":"10.1038","volume":"9","author":[{"given":"Yoon-Jung","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youhwa","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7323-0411","authenticated-orcid":false,"given":"Yeon-Hee","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungpyo","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4388-0338","authenticated-orcid":false,"given":"Hee-Kyung","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7534-5167","authenticated-orcid":false,"given":"Se-Young","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,27]]},"reference":[{"key":"54173_CR1","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1152\/physrev.1993.73.1.79","volume":"73","author":"BL Vallee","year":"1993","unstructured":"Vallee, B. L. & Falchuk, K. H. The biochemical basis of zinc physiology. Physiol Rev 73, 79\u2013118, https:\/\/doi.org\/10.1152\/physrev.1993.73.1.79 (1993).","journal-title":"Physiol Rev"},{"key":"54173_CR2","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1002\/glia.22286","volume":"60","author":"I Sekler","year":"2012","unstructured":"Sekler, I. & Silverman, W. F. Zinc homeostasis and signaling in glia. Glia 60, 843\u2013850, https:\/\/doi.org\/10.1002\/glia.22286 (2012).","journal-title":"Glia"},{"key":"54173_CR3","doi-asserted-by":"publisher","first-page":"16076","DOI":"10.1523\/JNEUROSCI.3454-11.2011","volume":"31","author":"SL Sensi","year":"2011","unstructured":"Sensi, S. L. et al. The neurophysiology and pathology of brain zinc. 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