{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T07:00:52Z","timestamp":1790406052631,"version":"4.1.0"},"reference-count":70,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:p> Previously, we demonstrated that genistein stimulated Cl<jats:sup>\u2212<\/jats:sup> secretion in the mouse jejunum (Baker MJ and Hamilton KL, Am J Physiol Cell Physiol 287: C1636\u2013C1645, 2004); however, the mode of action of genistein still remains unclear. Here, we examined the activation of Cl<jats:sup>\u2212<\/jats:sup> secretion by the modulation of phosphodiesterases (PDEs) by genistein (75 \u03bcM) in the mouse jejunum with the Ussing short-circuit current ( I<jats:sub>sc<\/jats:sub>) technique. Drugs tested included theophylline (10 mM), a nonspecific PDE inhibitor; 8-methoxymethyl-3-isobutyl-1-methylxanthine (8-MM-IBMX; 100 \u03bcM), erythro-9-(2-hydroxyl-3-nonyl)-adenine (EHNA; 40 \u03bcM), milrinone (100 \u03bcM), and rolipram (40 and 100 \u03bcM), which are specific inhibitors of PDE1\u2013PDE4, respectively. Theophylline stimulated a bumetanide-sensitive I<jats:sub>sc<\/jats:sub>, indicative of Cl<jats:sup>\u2212<\/jats:sup> secretion, and abolished genistein's stimulatory action on I<jats:sub>sc<\/jats:sub>. Neither 8-MM-IBMX nor EHNA altered the basal I<jats:sub>sc<\/jats:sub> nor did these PDE inhibitors affect the stimulatory action of genistein on the I<jats:sub>sc<\/jats:sub> of the mouse jejunum. Rolipram had no effect on basal I<jats:sub>sc<\/jats:sub>, but it reduced the genistein-stimulated I<jats:sub>sc<\/jats:sub> compared with time-matched control tissues. Milrinone stimulated a concentration-dependent increase in I<jats:sub>sc<\/jats:sub>. Bumetanide (10 \u03bcM) inhibited 60 \u00b1 4% of milrinone-induced I<jats:sub>sc<\/jats:sub>. Pretreating tissues with milrinone prevented genistein from stimulating I<jats:sub>sc<\/jats:sub>, and pretreatment with genistein reduced the effect of milrinone on I<jats:sub>sc<\/jats:sub>. H89 (50 \u03bcM), a PKA inhibitor, reduced the milrinone-stimulated I<jats:sub>sc<\/jats:sub>. Likewise, H89 reduced the genistein-stimulated I<jats:sub>sc<\/jats:sub>. Here, we demonstrate, for the first time, that genistein activates Cl<jats:sup>\u2212<\/jats:sup> secretion of the mouse jejunum via inhibition of a PDE3-dependent pathway. <\/jats:p>","DOI":"10.1152\/ajpcell.00152.2009","type":"journal-article","created":{"date-parts":[[2009,6,18]],"date-time":"2009-06-18T01:10:21Z","timestamp":1245287421000},"page":"C688-C698","source":"Crossref","is-referenced-by-count":10,"title":["Genistein stimulates electrogenic Cl<sup>\u2212<\/sup> secretion via phosphodiesterase modulation in the mouse jejunum"],"prefix":"10.1152","volume":"297","author":[{"given":"Pin-Chun","family":"Chao","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medical Sciences, University of Otago, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk L.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medical Sciences, University of Otago, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.06.051"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)01436-0"},{"key":"B3","unstructured":"Atteritano M , Mazzaferro S , Frisina A , Cannata ML , Bitto A , D'Anna R , Squadrito F , Macri I , Frisina N , Buemi M. 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