Springer Online Journal Archives 1860-2000
Abstract Hepatic bile synthesis is altered duringexperimental gallstone formation. In response tocholesterol, there is a hydrophobic shift in hepaticbile acid synthesis and hypersecretion of phospholipids.These changes decrease the vesicular capacity forcholesterol and favor crystallization. The mechanism forthese changes in hepatic bile formation is unknown.Calmodulin (CaM), a Ca2+ receptor proteininvolved in cellular secretion, regulates gallbladdertransport and may play an important role in alterationsof hepatic bile formation during cholelithiasis. Wehypothesized that biliary CaM activity is altered during gallstone formation and may beassociated with changes in bile acid and phospholipidsynthesis. Prairie dogs were fed either control (N = 22)or 1.2% cholesterol-enriched ( N 26) diets for one to six weeks. Cholecystectomy was performed; thecommon bile duct was cannulated, and hourly bile sampleswere collected. CaM was measured in bile and gallbladdertissues by radioimmunoassay. Bile samples were analyzed for cholesterol, phospholipids,total bile acids, total protein, calcium, and individualbile acid composition. Compared to controls, gallstoneanimals had elevated hepatic bile levels of CaM, phospholipids, and cholesterol.Hydrophobic bile acid synthesis was also stimulated,with increased levels of taurochenodeoxycholic acid(TCDCA) and decreased taurocholic acid (TCA).Gallbladder bile demonstrated similar changes. Althoughgallbladder bile CaM levels were increased, tissuelevels were unchanged, suggesting that increased CaMconcentration is a hepatic phenomenon. Hepatic bile CaMactivity correlated linearly with TCDCA concentration (r= 0.64, P 〈 0.004) and phospholipid hypersecretion (r= 0.53, P 〈 0.03). The relationship between biliaryCaM and increased concentrations of TCDCA andphospholipids suggests a role for CaM in alterations ofhepatocyte secretion that may promote gallstoneformation.
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