EVIDENCE FOR SECRETORY COUPLING OF PHOSPHATIDYLCHOLINE MOLECULAR-SPECIES TO CHOLESTEROL IN RAT BILE

Background/Aims: Hepatocytes secrete cholesterol into bile within lipi d vesicles of selected phosphatidylcholines, mainly palmitoyl-linoleoy l-phosphatidylcholines, palmitoleoyl-oleoyl-phosphatidylcholines and p almitoleoyl-arachidonyl-phosphatidylcholines, which could in part dete rmine the secreted amount of cholesterol. Aims: To study whether incre ased secretion of cholesterol, as caused by manipulation of cholestero l synthesis rate, changes the composition of phosphatidylcholines secr eted in bile. Methods: Livers from control rats (Control), rats fed pr avastatin for 7 days (Pravastatin) and livers isolated 5-7 or 8-11 hou rs after pravastatin had been withdrawn (Rebound(5-7 h); Rebound(8-11 h)) were isolated perfused during infusion of taurocholic acid (400 nm ol/min/100 g rat), to study biliary secretion of bile salts, cholester ol and phosphatidylcholine molecular species. Results: Bile salt secre tion rate was similar in all four groups, secretion of cholesterol and phosphatidylcholines was similar in Control and Pravastatin. With dur ation of pravastatin withdrawal the secretion rates of phosphatidylcho line and cholesterol progressively increased by +38% and +122% in Rebo und(5-7 h) and by +70% and +300% in Rebound(8-11 h) (vs Control), resp ectively, 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-linoleoyl -phospatidylcholines remained constant, The secretion rate of choleste rol was correlated (p<0.01) with the secretion rates of palmitoleoyl-o leoyl-phosphatidylcholines (r=0.83) and palmitoleoyl-arachidonyl-phosp hatidylcholines (r=0.81). Bilirubin ditaurate or taurodehydrocholate r educed (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 co-regulated with the amount of cholesterol destined for biliary secretion.