Abstract
The kinetics of uptake of [3H]ouabain were studied in hepatocytes isolated from livers of rats of various ages. Accumulation of ouabain in hepatocytes was measured at 1-min intervals for 4 min of incubation. Uptake of the drug was found to increase with the age of the animal. Although Vmax increased with age, there was no discernible difference in Km values. The uptake of [3H]ouabain into hepatocytes isolated from livers of 12-day-old rats could be stimulated by pretreatment of the animal with pregnenolone-16 alpha-carbonitrile. Uptake of [3H]taurocholate into isolated rat hepatocytes did not show a continuous age related pattern similar to that for ouabain. The age dependence of ouabain uptake into isolated rat hepatocytes demonstrated in this study is evidence that a low hepatic uptake capacity is the mechanism by which ouabain exhibits greater toxicity in the newborn rat.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|
