Effect of organic anions on biliary lipids in the rat

Bile salts enhance the biliary secretion of phospholipid and cholesterol. Other amphipilic molecules, organic anions, are secreted into bile as well. We studied the effects of bilirubin and iodipamide, two chemically dissimilar organic anions, on biliary lipid secretion in the rat. We infused bile salt pool-depleted rats with a stepwise infusion of taurocholate and a constant infusion of organic anion. Both organic anions markedly inhibited the biliary secretion of phospholipid and cholesterol without affecting bile salt secretion. This inhibition, at least with iodipamide, was dose-dependent and fully reversible. Using tritiated water as a precursor, we measured hepatic and biliary cholesterol synthesis in the presence or absence of an iodipamide infusion to see if decreased lipid synthesis could explain decreased secretion. Despite the marked reduction in biliary cholesterol secretion, the specific activity of biliary cholesterol was unchanged during an iodipamide infusion. We suggest that organic anions interfere with the assembly of the biliary mixed micelle resulting in micelles that are deficient in phospholipid and cholesterol.