cholecystokinin and Cholecystolithiasis

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.

Topics: Animals; Bile Acids and Salts; Cholecystitis; Cholecystokinin; Cholecystolithiasis; Fasting; Gallbladder; Gallbladder Diseases; Gallbladder Emptying; Humans; Muscle Contraction; Muscle, Smooth; Postprandial Period; Receptors, Cholecystokinin

The present investigation was undertaken to delineate the in vitro responsiveness of cholelithiatic gallbladders to cholecystokinin (CCK) and compared with those evoked by carbachol, histamine, or electrical stimulation. Gallbladder muscular strips (2-3 mm wide and 15-20 mm long) from patients undergoing cholecystectomy were used for recording the in vitro contractions evoked by electrical and chemical (carbachol, histamine, or cholecystokinin) stimulation. Stimulation of strips with trains of pulses (5-msec duration, 70 V at 100 Hz) of varying train durations (0.01 to 9 sec) elicited duration-dependent increase in the amplitude of contractions and the maximal contractions were seen with 5 sec. Atropine (0.4 microM) significantly attenuated these contractions, leaving about 34% of contractions, which in turn was abolished by xylocaine. Carbachol produced a concentration-dependent (0.004-0.4 microM) increase in force of contraction and the maximal response was seen at 0.4 microM and abolished by atropine (0.4 microM). Histamine also produced contractions and the maximal contractions were about 35% of the maximal carbachol response. Histamine-induced contractions were not abolished by atropine but were abolished by xylocaine. CCK up to 10 microM failed to evoke any contraction, even though the strips were responsive to carbachol. The results indicate that cholelithiatic gallbladders exhibited responses to electrical stimulation through cholinergic and histaminergic plexuses and they were insensitive to CCK.

Topics: Atropine; Carbachol; Cholecystokinin; Cholecystolithiasis; Cholinergic Agonists; Electric Stimulation; Gallbladder; Histamine; Humans; In Vitro Techniques; Muscle Contraction