THE POTENTIAL SITE OF IMPAIRED GALLBLADDER CONTRACTILITY IN AN ANIMAL-MODEL OF CHOLESTEROL GALLSTONE DISEASE

Background & Aims: Gallbladder contractility is decreased in cholester ol gallstone disease, but the mechanism underlining this defect is unc lear, The aim of this study was to determine the cellular site of this defect in an animal model of cholesterol gallstone disease, Methods: Ground squirrels were maintained for 28 days on either a control or a 1% cholesterol diet. Gallbladder contractile responses to several know n agonists were measured in vitro using smooth muscle strips. Results: Gallbladder contractility in response to cholecystokinin, bethanechol , and K+ was equally decreased in cholesterol-fed animals, in concert with an increased cholesterol saturation of gallbladder bile compared with controls, In contrast, the contractile responses to A-23187 (a ca lcium ionophore), cyclopiazonic acid (a selective, potent inhibitor of sarcoplasmic reticulum Ca2+ pump), and barium (a calcium analogue), w hich readily diffuse across the intact sarcolemmal membrane, remained the same in both groups, Dose responses to a G-protein activator, alum inum fluoride, were again not different between these two groups, Conc lusions: The primary smooth muscle defect in this animal model of chol esterol gallstone disease does not reside in the intracellular signal transduction pathways or in the contractile apparatus but instead invo lves the sarcolemmal membrane.