Cisapride improves gallbladder contractility and bile lipid composition in an animal model of gallstone disease.
BACKGROUND
The hepatic secretion of supersaturated bile and gallbladder stasis are key events in cholesterol gallstone formation. The therapeutic value of cisapride, a prokinetic agent, was assessed in ground squirrels on a 1% cholesterol diet.


METHODS
Biliary lipid secretion was measured directly and bile salt pool size assessed by isotope dilution ([14C]cholic acid). Gallbladder contraction was measured in vitro in response to cholecystokinin (CCK).


RESULTS
Cholesterol-fed animals had a combined hepatic secretory defect (a 53% decrease in bile salt secretion and also a 31% increase in cholesterol secretion). Adding cisapride restored bile salt secretion to control levels but did not affect cholesterol secretion. In cholesterol-fed animals, the cholesterol saturation index of gallbladder bile more than doubled and cholesterol crystals developed; cisapride markedly reduced cholesterol saturation, thus preventing crystal formation. Gallbladder contractility, measured in vitro in response to CCK, decreased 23% in animals on the 1% cholesterol diet; cisapride restored the CCK dose-response curve to normal. The bile salt pool as assessed by isotope dilution was similar in all groups.


CONCLUSIONS
Thus, lithogenic bile develops in this model because of reduced bile salt secretion and increased cholesterol secretion. Cisapride renders biliary lipid composition towards normal by enhancing gallbladder (and possibly intestinal) motility and cycling of the bile salt pool, thereby increasing bile salt secretion.
Xu
Q W
QW
Department of Medicine, Faculty of Medicine, University of Calgary, Alberta, Canada.
Shaffer
E A
EA
D000818:Animals; D001646:Bile / Q000737:chemistry*; D001647:Bile Acids and Salts / Q000378:metabolism; D002250:Carbon Radioisotopes; D002766:Cholecystokinin / Q000494:pharmacology; D002769:Cholelithiasis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D002793:Cholic Acids / Q000378:metabolism; D020117:Cisapride; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005704:Gallbladder / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005705:Gallbladder Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016473:Gallbladder Emptying / Q000187:drug effects / Q000502:physiology; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis*; D008297:Male; D010880:Piperidines / Q000627:therapeutic use*; D012589:Sciuridae; D012702:Serotonin Antagonists / Q000627:therapeutic use*
D001647:Bile Acids and Salts; D002250:Carbon Radioisotopes; D002791:Cholesterol, Dietary; D002793:Cholic Acids; D008055:Lipids; D010880:Piperidines; D012702:Serotonin Antagonists; D002766:Cholecystokinin; D020117:Cisapride