Stacey N H, Klaassen C D
J Pharmacol Exp Ther. 1979 Nov;211(2):360-3.
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.
研究了从不同年龄大鼠肝脏分离的肝细胞对[3H]哇巴因的摄取动力学。在孵育4分钟内,每隔1分钟测量肝细胞中哇巴因的积累量。发现药物的摄取随着动物年龄的增加而增加。虽然Vmax随年龄增加,但Km值没有明显差异。用孕烯醇酮-16α-腈预处理动物可刺激从12日龄大鼠肝脏分离的肝细胞对[3H]哇巴因的摄取。分离的大鼠肝细胞对[3H]牛磺胆酸盐的摄取没有显示出与哇巴因相似的与年龄相关的连续模式。本研究中证明的分离的大鼠肝细胞对哇巴因摄取的年龄依赖性表明,肝脏摄取能力低是哇巴因在新生大鼠中表现出更大毒性的机制。