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The aim of this study was to explore the mechanism of sodium sulphide (<jats:styled-content style=\"fixed-case\"><jats:roman>Na<jats:sub>2<\/jats:sub>S<\/jats:roman><\/jats:styled-content>)\u2010induced relaxation of rat uterus, investigate the importance of redox effects and ion channel\u2010mediated mechanisms, and any interactions between these two mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Organ bath studies were employed to assess the pharmacological effects of <jats:styled-content style=\"fixed-case\"><jats:roman>Na<jats:sub>2<\/jats:sub>S<\/jats:roman><\/jats:styled-content> in uterine strips by exposing them to <jats:styled-content style=\"fixed-case\"><jats:roman>Na<jats:sub>2<\/jats:sub>S<\/jats:roman><\/jats:styled-content> with or without <jats:styled-content style=\"fixed-case\"><jats:roman>Cl<jats:sup>\u2212<\/jats:sup><\/jats:roman><\/jats:styled-content> channel blockers (<jats:styled-content style=\"fixed-case\">DIDS<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">NFA<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">IAA<\/jats:styled-content>\u201094, <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>16<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>inh\u2010<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>01, <jats:styled-content style=\"fixed-case\">TA<\/jats:styled-content>), raised <jats:styled-content style=\"fixed-case\"><jats:roman>KCl<\/jats:roman><\/jats:styled-content> (15 and 75\u2009mM), <jats:styled-content style=\"fixed-case\"><jats:roman>K<jats:sup>+<\/jats:sup><\/jats:roman><\/jats:styled-content> channel inhibitors (glibenclamide, <jats:styled-content style=\"fixed-case\">TEA<\/jats:styled-content>, 4\u2010<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>\u2010type <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content> channel activator (<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>ay <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content> 8644), propranolol and methylene blue. The activities of antioxidant enzymes were measured in homogenates of treated uteri. The expression of bestrophin channel 1 (<jats:styled-content style=\"fixed-case\">BEST<\/jats:styled-content>\u20101) was determined by Western blotting and <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\"><jats:roman>Na<jats:sub>2<\/jats:sub>S<\/jats:roman><\/jats:styled-content> caused concentration\u2010dependent reversible relaxation of spontaneously active and calcium\u2010treated uteri, affecting both amplitude and frequency of contractions. Uteri exposed to 75\u2009mM <jats:styled-content style=\"fixed-case\"><jats:roman>KCl<\/jats:roman><\/jats:styled-content> were less sensitive to <jats:styled-content style=\"fixed-case\"><jats:roman>Na<jats:sub>2<\/jats:sub>S<\/jats:roman><\/jats:styled-content> compared with uteri in 15\u2009mM <jats:styled-content style=\"fixed-case\"><jats:roman>KCl<\/jats:roman><\/jats:styled-content>. <jats:styled-content style=\"fixed-case\"><jats:roman>Na<jats:sub>2<\/jats:sub>S<\/jats:roman><\/jats:styled-content>\u2010induced relaxations were abolished by DIDS, but unaffected by other modulators or by the absence of extracellular <jats:styled-content style=\"fixed-case\"><jats:roman>HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup><\/jats:roman><\/jats:styled-content>, suggesting the involvement of chloride ion channels. <jats:styled-content style=\"fixed-case\"><jats:roman>Na<jats:sub>2<\/jats:sub>S<\/jats:roman><\/jats:styled-content> in combination with different modulators provoked specific changes in the anti\u2010oxidant profiles of uteri. The expression of <jats:styled-content style=\"fixed-case\">BEST<\/jats:styled-content>\u20101, both <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein, was demonstrated in rat uteri.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>The relaxant effects of <jats:styled-content style=\"fixed-case\"><jats:roman>Na<jats:sub>2<\/jats:sub>S<\/jats:roman><\/jats:styled-content> in rat uteri are mediated mainly via a <jats:styled-content style=\"fixed-case\">DIDS<\/jats:styled-content>\u2010sensitive <jats:styled-content style=\"fixed-case\"><jats:roman>Cl<jats:sup>\u2212<\/jats:sup><\/jats:roman><\/jats:styled-content>\u2010pathway. Components of the relaxation are redox\u2010 and <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>\u2010dependent.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13161","type":"journal-article","created":{"date-parts":[[2015,4,8]],"date-time":"2015-04-08T10:06:45Z","timestamp":1428487605000},"page":"3671-3686","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Chloride channels mediate sodium sulphide\u2010induced relaxation in rat uteri"],"prefix":"10.1111","volume":"172","author":[{"given":"Ana","family":"Miju\u0161kovi\u0107","sequence":"first","affiliation":[{"name":"Department of Physiology Institute for Biological Research \u2018Sini\u0161a Stankovi\u0107\u2032 University of Belgrade  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra 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