[Different effect of taurolithocholate and chenodeoxycholate on structure and function of isolated hepatocytes...

Alterations of cellular membranes under the influence of bile acids seem to be of pathophysiological importance in cholestasis. The effect of taurolithocholic acid (TLCA) and chenodeoxycholic acid (CDCA) on membrane structure and release of cellular enzymes was studied on isolated rat hepatocytes. The response of urea synthesis to glucagon was used as a parameter of membrane function. The threshold dose of TLCA, marked by rapidly increasing enzyme release, was about 100 micrometers, whereas that of CDCA was between 500 and 1,000 micrometers. Addition of albumin (1 g-%) increased the threshold dose of CDCA; this occurred for TLCA only 8 g-%. Electron-microscopical alterations of the endoplasmic reticulum and submembranous areas were found with concentrations below these threshold doses even in the presence of albumin. These alterations are interpreted as disturbance of cellular transport and energy metabolism. TLCA inhibited glucagon response of cells in concentrations below 100 micrometers. These results demonstrate an influence of the bile acids studied on structure and function of liver cell membranes, which may be of importance in the pathogenesis of cholestasis. The rough endoplasmic reticulum could be another cellular structure which is affected by these bile acids.