Biliary secretion of ouabain-3H and its uptake by liver slices in the rat

Abstract

Ouabain-3H, administered intravenously (1 mg/kg) to rats with ligated renal pedicles, is rapidly excreted in the bile in high concentrations as the unchanged compound. Between 5 and 60 min. after administration, the bile-to-plasma concentration ratio of the glycoside is 147-557, and 85% of the administered dose is excreted in 90 min. The drug is also concentrated in hepatic tissue, the liver-to-plasma ratio being 33-117. The rate of biliary excretion of ouabain is not depressed by large doses of various organic anions or cations. Rat liver slices, incubated aerobically at 37 C with 1 x 10-5 M ouabain-3H, take up the glycoside against an apparent concentration gradient of about 4-fold. The uptake process appears to be saturable and is inhibited by anaerobic conditions, a number of metabolic inhibitors, and a number of cardiac glycosides. Ouabain does not appear to be bound to components of rat liver homogenates. Ouabain is taken up by the liver and excreted into bile by active transport process, and the process is different from those which transport a number of organic anions and cations.