THE POTENTIAL SITE OF DISORDERED GALLBLADDER CONTRACTILITY DURING THEEARLY-STAGE OF CHOLESTEROL GALLSTONE FORMATION

BACKGROUND/AIMS: Feeding a high cholesterol diet to dogs causes a redu ction in gallbladder smooth muscle contractility with a consequent sta sis. Gallbladder stasis is an important link between the hepatic secre tion of cholesterol saturated bile and the formation of cholesterol ga llstones. METHODOLOGY: In this study we tried to localize the probable site of gallbladder smooth muscle dysfunction in a well established a nimal model of cholesterol gallstone disease. Adult male dogs were fed either a high or low cholesterol diet (control group). Strips of gall bladder smooth muscle for tension development were stimulated with two groups of agonists and dose response curves were plotted for all agon ists used. RESULTS: The forces developed in response to the first grou p of agonists, the cell membrane-active agonists, e.g. acetylcholine, cholecystokinin, add potassium chloride were decreased in high cholest erol fed dogs with an increased cholesterol saturation of bile when co mpared to the control group. On the other hand, the contractile respon se showed non-significant differences between the test and the control group on using the second group of agonists that bypass the intact sa rcolemmal membrane and stimulate directly either the contractile mecha nism, e.g. barium, or the intracellular signal transduction pathways e .g. aluminum fluoride. CONCLUSION: We conclude that the smooth muscle defect responsible for disordered gallbladder contractility in high ch olesterol fed dogs most probably involves the sarcolemmal membrane.