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However, there is no evidence of the bradykinin receptors and their functions in human salivary glands. Here we have identified and characterized bradykinin receptors on human submandibular gland cells. Both bradykinin B1 and B2 receptors are expressed on human submandibular gland cells, A253 cells, and HSG cells. Bradykinin increased the intracellular Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) in a concentration\u2010dependent manner. Interestingly, a specific agonist of the B1 receptor did not have any effect on [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in <jats:styled-content style=\"fixed-case\">HSG<\/jats:styled-content> cells, whereas specific agonists of the B2 receptor had a Ca<jats:sup>2+<\/jats:sup> mobilizing effect. Furthermore, application of the B1 receptor antagonist, R715, did not alter the bradykinin\u2010mediated increase in cytosolic Ca<jats:sup>2+<\/jats:sup>, whereas the B2 receptor antagonist, <jats:styled-content style=\"fixed-case\">HOE<\/jats:styled-content>140, showed a strong inhibitory effect, which implies that bradykinin B2 receptors are functional in modulating the concentration of cytosolic Ca<jats:sup>2+<\/jats:sup>. Bradykinin did not affect a carbachol\u2010induced rise of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> and did not modulate translocation of aquaporin\u20105. However, bradykinin did promote the expression of proinflammatory cytokines, including tumor necrosis factor\u2010<jats:italic>\u03b1<\/jats:italic> (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010<jats:italic>\u03b1<\/jats:italic>), implying the role of bradykinin in salivary gland inflammation. These data suggest that bradykinin receptors are involved in Ca<jats:sup>2+<\/jats:sup> signaling in human submandibular gland cells and serve a unique role, which is separate from that of other salivary gland G protein\u2013coupled receptors.<\/jats:p>","DOI":"10.1111\/eos.12324","type":"journal-article","created":{"date-parts":[[2016,12,29]],"date-time":"2016-12-29T11:49:28Z","timestamp":1483012168000},"page":"18-27","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Human salivary gland cells express bradykinin receptors that modulate the expression of proinflammatory cytokines"],"prefix":"10.1111","volume":"125","author":[{"given":"Keimin","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Physiology Dental Research Institute Seoul National University School of Dentistry Seoul 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