{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T11:59:34Z","timestamp":1779105574371,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3103,"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":[[2000,8]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The flavonoid genistein has been shown to activate a Cl<jats:sup>\u2212<\/jats:sup> conductance in various cell types expressing CFTR. We examined if similar effects can be observed when genistein is applied to native <jats:italic>ex vivo<\/jats:italic> tissues from human respiratory tract and rectum. We further compared the effects when genistein was applied to oocytes of <jats:italic>Xenopus laevis<\/jats:italic> expressing CFTR.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In oocytes, both wtCFTR and \u0394F508\u2010CFTR were activated by genistein while both cyclic AMP (K<jats:sub>v<\/jats:sub>LQT1) and Ca<jats:sup>2+<\/jats:sup> (SK4) activated K<jats:sup>+<\/jats:sup> channels were inhibited at high concentrations of genistein.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Biopsies from nasal polyps and rectal mucosa were obtained from normal individuals (non\u2010CF) and CF patients and in the presence of amiloride (10\u2003\u03bcmol\u2003l<jats:sup>\u22121<\/jats:sup>; mucosal side) the effects of genistein were assessed using a perfused Ussing chamber. In non\u2010CF airway epithelia, genistein (50\u2003\u03bcmol\u2003l<jats:sup>\u22121<\/jats:sup>; mucosal side) increased lumen negative I<jats:sub>sc<\/jats:sub> but had no additional effects on tissues pre\u2010stimulated with IBMX and forskolin (100\u2003\u03bcmol\u2003l<jats:sup>\u22121<\/jats:sup> and 1\u2003\u03bcmol\u2003l<jats:sup>\u22121<\/jats:sup>; both sides).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In non\u2010CF rectal biopsies, in the presence of amiloride (10\u2003\u03bcmol\u2003l<jats:sup>\u22121<\/jats:sup>; mucosal side) and indomethacin (10\u2003\u03bcmol\u2003l<jats:sup>\u22121<\/jats:sup>; basolateral side), genistein increased lumen negative I<jats:sub>sc<\/jats:sub> and enabled cholinergic (carbachol; CCH, 100\u2003\u03bcmol\u2003l<jats:sup>\u22121<\/jats:sup>; basolateral side) stimulation of Cl<jats:sup>\u2212<\/jats:sup> secretion indicating activation of luminal CFTR Cl<jats:sup>\u2212<\/jats:sup> channels. However, after stimulation with IBMX\/forskolin, genistein induced opposite effects and significantly inhibited CCH activated I<jats:sub>sc<\/jats:sub>. In CF airway and intestinal tissues genistein failed to induce Cl<jats:sup>\u2212<\/jats:sup> secretion.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Thus, genistein is able to activate luminal CFTR Cl<jats:sup>\u2212<\/jats:sup> conductance in non\u2010CF tissues and mutant CFTR in oocytes. However, additional inhibitory effects on basolateral K<jats:sup>+<\/jats:sup> conductance and missing effects in native CF tissues do not support the use for pharmacological intervention in CF.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>130<\/jats:bold>, 1884\u20131892; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703520\">10.1038\/sj.bjp.0703520<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703520","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:46:59Z","timestamp":1106945219000},"page":"1884-1892","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Effect of genistein on native epithelial tissue from normal individuals and CF patients and on ion channels expressed in <i>Xenopus<\/i> oocytes"],"prefix":"10.1111","volume":"130","author":[{"given":"Marcus","family":"Mall","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Wissner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans H","family":"Seydewitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"H\u00fcbner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Kuehr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Brandis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rainer","family":"Greger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Kunzelmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.39.27415"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.268.1.C154"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1988.sp017322"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1998.275.5.G1166"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6739"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00832-2"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"C747","DOI":"10.1152\/ajpcell.1997.273.2.C747","article-title":"Genistein activates CFTR Cl\u2010 channels via a tyrosine kinase\u2010 and protein phosphatase\u2010independent mechanism","volume":"273","author":"FRENCH P.J.","year":"1997","journal-title":"Am. 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