{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:58:05Z","timestamp":1784228285945,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,5,24]],"date-time":"2012-05-24T00:00:00Z","timestamp":1337817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background\u2002<\/jats:bold> Decreased gallbladder smooth muscle (GBSM) contractility is a hallmark of cholesterol gallstone disease, but the interrelationship between lithogenicity, biliary stasis, and inflammation are poorly understood. We studied a mouse model of gallstone disease to evaluate the development of GBSM dysfunction relative to changes in bile composition and the onset of sterile cholecystitis.<\/jats:p><jats:p><jats:bold>Methods\u2002<\/jats:bold> BALB\/cJ mice were fed a lithogenic diet for up to 8\u2003weeks, and tension generated by gallbladder muscle strips was measured. Smooth muscle Ca<jats:sup>2+<\/jats:sup> transients were imaged in intact gallbladder.<\/jats:p><jats:p><jats:bold>Key Results\u2002<\/jats:bold> Lipid composition of bile was altered lithogenically as early as 1\u2003week, with increased hydrophobicity and cholesterol saturation indexes; however, inflammation was not detectable until the fourth week. Agonist\u2010induced contractility was reduced from weeks 2 through 8. GBSM normally exhibits rhythmic synchronized Ca<jats:sup>2+<\/jats:sup> flashes, and their frequency is increased by carbachol (3\u2003\u03bc<jats:sc>m<\/jats:sc>). After 1\u2003week, lithogenic diet\u2010fed mice exhibited disrupted Ca<jats:sup>2+<\/jats:sup> flash activity, manifesting as clustered flashes, asynchronous flashes, or prolonged quiescent periods. These changes could lead to a depletion of intracellular Ca<jats:sup>2+<\/jats:sup> stores, which are required for agonist\u2010induced contraction, and diminished basal tone of the organ. Responsiveness of Ca<jats:sup>2+<\/jats:sup> transients to carbachol was reduced in mice on the lithogenic diet, particularly after 4\u20138\u2003weeks, concomitant with appearance of mucosal inflammatory changes.<\/jats:p><jats:p><jats:bold>Conclusions &amp; Inferences\u2002<\/jats:bold> These observations demonstrate that GBSM dysfunction is an early event in the progression of cholesterol gallstone disease and that it precedes mucosal inflammation.<\/jats:p>","DOI":"10.1111\/j.1365-2982.2012.01935.x","type":"journal-article","created":{"date-parts":[[2012,5,24]],"date-time":"2012-05-24T09:18:10Z","timestamp":1337851090000},"source":"Crossref","is-referenced-by-count":56,"title":["Disruption of gallbladder smooth muscle function is an early feature in the development of cholesterol gallstone disease"],"prefix":"10.1111","volume":"24","author":[{"given":"B.","family":"Lavoie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Nausch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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