{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:33:31Z","timestamp":1785537211057,"version":"3.56.0"},"reference-count":72,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2014,6,25]],"date-time":"2014-06-25T00:00:00Z","timestamp":1403654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Suramin is a clinically prescribed drug for treatment of human<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>frican trypanosomiasis, cancer and infection. It is also a well\u2010known pharmacological antagonist of<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>2 purinoceptors. Despite its clinical use and use in research, the biological actions of this molecule are still incompletely understood. Here, we investigated the effects of suramin on membrane channels, as exemplified by its actions on non\u2010junctional connexin43 (<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>x43) hemichannels, pore\u2010forming \u03b1\u2010haemolysin and channels involved in<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>release under hypotonic conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Hemichannels were activated by removing extracellular<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>. The influences of suramin on hemichannel activities were evaluated by its effects on influx of fluorescent dyes and efflux of<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>. The membrane permeability and integrity were assessed through cellular retention of preloaded calcein and<jats:styled-content style=\"fixed-case\">LDH<\/jats:styled-content>release.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Suramin blocked<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>x43 hemichannel permeability induced by removal of extracellular<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>without much effect on<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>x43 expression and gap junctional intercellular communication. This action of suramin was mimicked by its analogue<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>023 and<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>449 but not by another<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>2 purinoceptor antagonist<jats:styled-content style=\"fixed-case\">PPADS<\/jats:styled-content>. Besides hemichannels, suramin also significantly blocked intracellular and extracellular exchanges of small molecules caused by \u03b1\u2010haemolysin from<jats:styled-content style=\"fixed-case\"><jats:italic>S<\/jats:italic><\/jats:styled-content><jats:italic>taphylococcus aureus<\/jats:italic>and by exposure of cells to hypotonic solution. Furthermore, it prevented \u03b1\u2010haemolysin\u2010 and hypotonic stress\u2010elicited cell injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Suramin blocked membrane channels and protected cells against toxin\u2010 and hypotonic stress\u2010elicited injury. Our finding provides novel mechanistic insights into the pharmacological actions of suramin. Suramin might be therapeutically exploited to protect membrane integrity under certain pathological situations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12693","type":"journal-article","created":{"date-parts":[[2014,3,18]],"date-time":"2014-03-18T10:58:36Z","timestamp":1395140316000},"page":"3448-3462","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Suppression of cell membrane permeability by suramin: involvement of its inhibitory actions on connexin 43 hemichannels"],"prefix":"10.1111","volume":"171","author":[{"given":"Yuan","family":"Chi","sequence":"first","affiliation":[{"name":"Department of Molecular Signaling Interdisciplinary Graduate School of Medicine and Engineering University of Yamanashi Chuo Yamanashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Molecular Signaling Interdisciplinary Graduate School of Medicine and Engineering University of Yamanashi Chuo Yamanashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular Signaling Interdisciplinary Graduate School of Medicine and Engineering University of Yamanashi Chuo Yamanashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering University of Yamanashi Chuo Yamanashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Molecular Signaling Interdisciplinary Graduate School of Medicine and Engineering University of Yamanashi Chuo Yamanashi 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