Smooth muscle function and dysfunction in gallbladder disease

Abstract

The gallbladder epithelium and smooth muscle layer are exposed to concentrated biliary solutes, including cholesterol and potentially toxic hydrophobic bile salts, which are able to influence muscle contraction. Physiologically, gallbladder tone is regulated by spontaneous muscle activity, hormones, and neurotransmitters released into the muscle from intrinsic neurons and extrinsic sympathetic nerves. Methods to explore gallbladder smooth muscle function in vitro include cholecystokinin (CCK) receptor-binding studies and contractility studies. In human and animal models, studies have focused on cellular and molecular events in health and disease, and in vitro findings mirror in vivo events. The interplay between contraction and relaxation of the gallbladder muscularis leads in vivo to appropriate gallbladder emptying and refilling during fasting and postprandially. Defective smooth muscle contractility and/or relaxation are found in cholesterol stone-containing gallbladders, featuring a type of gallbladder leiomyopathy; defects of CCKA receptors and signal transduction may coexist with abnormal responses to oxidative stress and inflammatory mediators. Abnormal smooth musculature contractility, impaired gallbladder motility, and increased stasis are key factors in the pathogenesis of cholesterol gallstones.