Intracellular supply of phospholipids for biliary secretion: Evidence for a nonvesicular transport component

Phospholipids (PL) for biliary secretion could be supplied from the endopla smic reticulum (ER) to the plasma membrane by cytosolic transfer proteins o r transport vesicles. Therefore, we studied whether biliary secretions of P L and apolipoprotein A-I (apo A-I), as markers for the ER-to-Golgi vesicula r transport pathway, are tightly coupled in isolated perfused rat livers wi th enhanced secretion (+60%) of PL after withdrawal of the cholesterol synt hesis inhibitor pravastatin (0.1% of chow, fed for 7 days). Blocking agents dissociated the secretion of apo A-I and FL. Brefeldin A as well as cycloh eximide inhibited biliary secretion of apo A-I (-52%; -68%), however, not o f FL, Both bilirubin ditaurate and taurodehydrocholic acid reduced biliary secretion of PL (-27%; -79%), but not of apo A-I. The data support the conc ept that PL destined for biliary secretion bypass the vesicular transport p athway of apo A-I through the Golgi compartment, most likely via cytosolic transfer proteins. (C) 2000 Academic Press.