Effect of colchicine and S,S,S-tributyl phosphorotrithioate (DEF) on the biliary excretion of sucrose, mannitol and horseradish peroxidase in the rat.

The purpose of this study was to demonstrate the effect of colchicine and S,S,S-tributyl phosphorotrithioate (DEF) on vesicular transport of horseradish peroxidase (HRP) into bile at the same time that permeability changes occur in the canalicular membrane. Anesthetized Sprague-Dawley rats were surgically prepared with a bile duct cannulae. Four hours after colchicine pretreatment (10 mg/kg, i.p.), biliary excretion of intravenously injected sucrose and mannitol was increased, while that of HRP was decreased. Administration of these marker compounds from the bile side by segmented retrograde intrabiliary injection (SRII) (40 microliters washed in the 110 microliters saline) resulted in decreased biliary excretion of all three markers in colchicine-pretreated rats. Twenty minutes after DEF pretreatment by intrabiliary administration (40 microliters of DEF washed in with 31 microliters of saline and held in place for 0.5 min), the biliary excretion of intravenously injected sucrose and mannitol was decreased but that of HRP was increased; when administered by SRII, the biliary excretion of all three marker compounds was increased. These results demonstrate that colchicine, in addition to having blocked vesicular transport (HRP), also increased canalicular permeability to sucrose and mannitol. DEF, on the other hand, decreased canalicular permeability to sucrose and mannitol and enhanced vesicular transport of HRP.