Selective biliary secretion of basal and glucagon-inhibited neutral sterol after triparanol administration

Biliary cholesterol secretion was studied in dogs with chronic bile fistulas, using glucagon, an inhibitor of biliary cholesterol secretion, and triparanol, an inhibitor of cholesterol synthesis. Glucagon inhibited neutral sterol secretion before and after triparanol administration. Triparanol caused a significant accumulation in bile of the cholesterol precursor desmosterol which comprised a significant portion of the neutral sterol in bile but not in blood. Glucagon inhibited both biliary desmosterol and cholesterol secretions to a similar degree. These findings suggest that biliary cholesterol is derived from newly synthesized hepatic sterol as well as from equilibrated sources. Furthermore, glucagon suppressed biliary secretion of both equilibrated as well as newly synthesized neutral sterol, suggesting that glucagon inhibits the movement of neutral sterol to or through the canalicular membrane.