Abstract

Due to the biliary excretion of ouabain in rats, a specialized transport process has been proposed for the excretion of organic neutral compounds. In the present study, ³H-ouabain (0.08 mg/kg) was administered i.v. to rats, rabbits and dogs and the plasma disappearance and biliary excretion of ³H was measured over a 12-hour period. Ouabain disappeared from the plasma much more rapidly in the rat than in the other two species. Ouabain was also excreted into the bile at a much higher rate by the rat (900 mµg/min/kg) than by the rabbit or dog (20 and 5 mµg/min/kg). In an attempt to explain the above species difference, the plasma, bile and liver concentration ³H was determined 20 minutes after ³H-ouabain was administered. The rat exhibited an overall bile to plasma concentration gradient of 1500, whereas the same gradient was much less for the rabbit (2.9) and dog (9.3). The liver/plasma and bile/liver gradients were both much greater in the rat (20 and 71) than in the rabbit (2.5 and 1.3) or dog (3.3 and 2.7). It would appear that the relative inability of the rabbit and dog to excrete ouahain into the bile is due to a low capacity for transferring ouabain from the plasma to liver and from the liver to bile. This species variation in the biliary excretion of ouabain appears to be an important factor in the resistance of the rat to the toxic effects of ouabain relative to the rabbit and dog.