Protoporphyrin IX-induced impairment of biliary lipid secretion in the rat

1. In order to gain information on the effect of protoporphyrin IX on changes in the properties of the canalicular plasma membrane, we studied the release of canalicular membrane constituents, namely phospholipids, cholesterol and 5'-nucleotidase, into bile in anaesthetized rats receiving saline or taurocholate (0.5 mumol min-1 100 g-1 body weight) with or without protoporphyrin IX infusion (10 or 20 micrograms min-1 100 g-1 body weight). 2. Protoporphyrin IX induced an impairment of spontaneous bile flow and of biliary secretion of cholesterol, phospholipids and bile acids. The taurocholate-induced increase in bile acid output was not significantly reduced by protoporphyrin IX at either of the doses used. However, when a cholestatic dose of protoporphyrin IX was infused, the taurocholate-induced bile flow and secretion of lecithin and cholesterol were significantly reduced. 3. Biliary output of phospholipid species other than lecithin did not counterbalance the protoporphyrin IX-induced reduction in biliary lecithin secretion. Biliary outputs of both total phospholipid and lecithin were inhibited by protoporphyrin IX to similar extents. 4. Protoporphyrin IX alone had no effect on the biliary release of 5'-nucleotidase, whereas when it was given with taurocholate, it increased the bile acid-induced biliary output of this enzyme markedly. 5. In summary, these results indicate that protoporphyrin IX impairs the biliary secretion of phospholipids and cholesterol but not that of bile acid. The release of canalicular membrane constituents other than lipids was also modified by protoporphyrin IX.