In recent clinical and animal experimental studies,
ursodeoxycholic acid (UDCA) has been noted to have marked choleretic and cytoprotective actions. To define the mechanism and determine whether such favorable influence is specific to UDCA, the choleretic action of
beta-muricholic acid (beta-MCA), which has a similar chemical structure, was studied using an isolated rat-liver-perfusion system. As a result, beta-MCA and
taurine-conjugated beta-MCA (T beta-MCA) stimulated bile flow accompanied by elevation of
bile acid output and
phospholipid output, and beta-MCA caused an elevation in biliary HCO3- concentration in normal rat livers. After
colchicine treatment,
taurocholic acid (TCA) administration was associated with marked
cholestasis while both beta-MCA and T beta-MCA still increased bile flow under the same conditions. Furthermore, simultaneous administration of beta-MCA or, more markedly, T beta-MCA reversed the effects of TCA alone in
colchicine-treated rat liver; significant preventive effects against the
cholestasis could be shown. These data suggest that beta-MCA and especially T beta-MCA can support choleresis even under conditions of
colchicine-dependent microtubule dysfunction. The effects of T beta-MCA on organelle
lipids and their intracellular transport may differ from those of TCA, presumably because of the anticholestatic and cytoprotective effects of T beta-MCA.