{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:03:11Z","timestamp":1790402591980,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2016,10,4]],"date-time":"2016-10-04T00:00:00Z","timestamp":1475539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL034215"],"award-info":[{"award-number":["HL034215"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) modulates many pathophysiological processes, including inflammation and allergic reactions, in which mast cells act as major effector cells. IgE receptor (Fc\u03b5RI) cross linking leads to an increase in intracellular calcium ([Ca<jats:sup>+2<\/jats:sup>]<jats:sub>i<\/jats:sub>), a critical step in mast cell degranulation. The aim of this study was to investigate the role of H<jats:sub>2<\/jats:sub>S in [Ca<jats:sup>+2<\/jats:sup>]<jats:sub>i<\/jats:sub>\u2010dependent mast cell activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We investigated the effects of H<jats:sub>2<\/jats:sub>S, either endogenously produced or released by the slow H<jats:sub>2<\/jats:sub>S donor 4\u2010carboxy\u2010phenyl isothiocyanate (PhNCS\u2010COOH), on antigenic\u2010 and non\u2010antigenic degranulation of native murine mast cells, and human and rat (RBL\u20102H3) mast cell lines. We measured the release of specific mast cell degranulation markers (\u03b2\u2010hexosaminidase and renin), as well as changes in [Ca<jats:sup>+2<\/jats:sup>]<jats:sub>i<\/jats:sub> and phosphorylation of proteins downstream of Fc\u03b5RI activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Endogenously produced H<jats:sub>2<\/jats:sub>S inhibited antigen\u2010induced degranulation in RBL\u20102H3. Similarly, H<jats:sub>2<\/jats:sub>S released by PhNCS\u2010COOH (10\u2013300\u00a0\u03bcM) reduced, in a concentration\u2010dependent manner, antigenic and non\u2010antigenic degranulation and renin release in all mast cell types. Notably, PhNCS\u2010COOH also prevented in a concentration\u2010dependent mode the increase in [Ca<jats:sup>+2<\/jats:sup>]<jats:sub>i<\/jats:sub> elicited by Ca<jats:sup>+2<\/jats:sup> ionophore, thapsigargin and Fc\u03b5RI activation. Moreover, PhNCS\u2010COOH attenuated the phosphorylation of Syk, cPLA\u20102 and PLC\u03b31 in antigen\u2010stimulated RBL\u20102H3 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Collectively, our results demonstrate that, by attenuating the phosphorylation of proteins downstream of Fc\u03b5RI cross\u2010linking on mast cells, H<jats:sub>2<\/jats:sub>S diminishes [Ca<jats:sup>+2<\/jats:sup>]<jats:sub>i<\/jats:sub> availability and thus mast cell degranulation and renin release. These findings suggest that PhNCS\u2010COOH could be a strategic therapeutic tool in mast cell\u2010mediated allergic conditions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13583","type":"journal-article","created":{"date-parts":[[2016,8,22]],"date-time":"2016-08-22T23:26:44Z","timestamp":1471908404000},"page":"3222-3234","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["The novel H<sub>2<\/sub>S donor 4\u2010carboxy\u2010phenyl isothiocyanate inhibits mast cell degranulation and renin release by decreasing intracellular calcium"],"prefix":"10.1111","volume":"173","author":[{"given":"Alice","family":"Marino","sequence":"first","affiliation":[{"name":"Department of Pharmacology Weill Cornell Medicine  New York NY 10065 USA"},{"name":"Department of Pharmacy University of Pisa  56126 Pisa 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