Background & aims: Gallbladder contractility is decreased in cholesterol gallstone disease, but the mechanism underlining this defect is unclear. 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 known 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 calcium ionophore), cyclopiazonic acid (a selective, potent inhibitor of sarcoplasmic reticulum Ca2+ pump), and barium (a calcium analogue), which readily diffuse across the intact sarcolemmal membrane, remained the same in both groups. Dose responses to a G-protein activator, aluminum fluoride, were again not different between these two groups.
Conclusions: The primary smooth muscle defect in this animal model of cholesterol gallstone disease does not reside in the intracellular signal transduction pathways or in the contractile apparatus but instead involves the sarcolemmal membrane.