Evidence for secretory coupling of phosphatidylcholine molecular species to cholesterol in rat bile.

BACKGROUND/AIMS: Hepatocytes secrete cholesterol into bile within lipid vesicles of selected phosphatidylcholines, mainly palmitoyl-linoleoyl-phosphatidylcholines, palmitoleoyl-oleoyl-phosphatidylcholines and palmitoleoyl-arachidonyl-phosphatidylcholines, which could in part determine the secreted amount of cholesterol.

AIMS

To study whether increased secretion of cholesterol, as caused by manipulation of cholesterol synthesis rate, changes the composition of phosphatidylcholines secreted in bile.

METHODS

Livers from control rats (Control), rats fed pravastatin for 7 days (Pravastatin) and livers isolated 5-7 or 8-11 hours after pravastatin had been withdrawn (Rebound5-7h; Rebound8-11h) were isolated perfused during infusion of taurocholic acid (400 nmol/min/100 g rat), to study biliary secretion of bile salts, cholesterol and phosphatidylcholine molecular species.

RESULTS

Bile salt secretion rate was similar in all four groups, secretion of cholesterol and phosphatidylcholines was similar in Control and Pravastatin. With duration of pravastatin withdrawal the secretion rates of phosphatidylcholine and cholesterol progressively increased by +38% and +122% in Rebound5-7h and by +70% and +300% in Rebound8-11h (vs Control), respectively. In parallel, the secretion rates of palmitoleoyl-oleoyl- and palmitoleoyl-arachidonyl-phosphatidylcholines rose up to sixfold and twofold, respectively, while the secretion rate of palmitoyl-linoleoylphospatidylcholines remained constant. The secretion rate of cholesterol was correlated (p < 0.01) with the secretion rates of palmitoleoyl-oleoyl-phosphatidylcholines (r = 0.83) and palmitoleoyl-arachidonyl-phosphatidylcholines (r = 0.81). Bilirubin ditaurate or taurodehydrocholate reduced (p < 0.05) biliary secretion of phosphatidylcholines (-33%; -72%) without changes in cholesterol/phosphatidylcholine secretory ratio or phosphatidylcholine species.

CONCLUSIONS

The secretion of the major molecular species of phosphatidylcholine in bile could be coregulated with the amount of cholesterol destined for biliary secretion.