Partial characterization of regulation of biliary lecithin hydrophobicity: association with organic anion-induced solute cholestasis in rats

We examined the effects of the depletion of bile salts and of the intravenous infusion of sodium taurocholate (STC) with or without bromosulphophthalein (BSP) in rats on the biliary secretion of lipids to clarify the regulatory mechanism(s). Each rat was equipped with a bile-duct cannula to collect bile. After the endogenous bile salt pool was depleted, STC was infused at a constant rate (160 nmol/min per 100 g body wt.) with or without BSP (50, 100, or 150 nmol/min per 100 g body wt.). BSP reduced the biliary secretion of cholesterol and phospholipids dose-dependently without affecting the secretion of bile salts (uncoupling phenomenon). Compared with the physiological and STC-infused condition, the biliary cholesterol/phospholipid ratio and saturated/unsaturated fatty acid ratio increased under the bile salts depletion and uncoupling phenomenon. Data indicate that the hydrophobicity of biliary lecithin increases with a decrease in the bile salt micelle capacity to induce biliary lipid secretion, resulting in a higher packing density of biliary vesicle. The cholesterol-holding capacity of the biliary vesicle is therefore enhanced during the depletion of bile salts and the uncoupling phenomenon.

Distribution and monomer activity of cholesterol in micellar bile salt: effect of cholesterol level

Despite the fact that uptake of cholesterol by the enterocyte occurs as a monomer from the intermicellar aqueous phase in equilibrium with micelle, the cholesterol monomer concentration in the aqueous phase and the partition coefficient between intermicellar aqueous phase and micellar aggregate have not been clarified. The present study deals with the distribution of cholesterol and monomer activity in constant bile salt-fatty acid micellar solutions with different cholesterol concentrations. In addition, uptake of cholesterol from these micellar solutions into rat jejunum was studied using everted sacs. Cholesterol monomer concentration in the aqueous phase increased linearly with the concentration of cholesterol in the micellar solution. Partition coefficient of cholesterol between the aqueous phase surrounding micelle and micellar aggregate was essentially constant at any cholesterol level (K = 3 X 10(-2)). Cholesterol monomer activities were linearly proportional to the cholesterol concentrations in the micellar solutions and correlated well with the rate of cholesterol uptake. It is concluded from these experiments that a partitioning phenomenon determines cholesterol monomer concentrations in the intermicellar aqueous phase from which the cholesterol is absorbed. After disappearance of the cholesterol monomers from the aqueous phase, these monomers are replaced by a shift of monomers from the intramicelle to intermicellar aqueous phase, under constant partition coefficient between extra- and intramicelle. The bile salt micelle provides a huge reservoir for partitioning of cholesterol monomers.