Lidocaine uptake in isolated rat hepatocytes and effects of dl-propranolol.
Lidocaine uptake in isolated rat hepatocytes and effects of dl-propranolol.
复制标题
离体大鼠肝细胞中利多卡因的摄取和 dl-普萘洛尔的影响。
DOI：
10.1016/0041-008x(80)90232-x
复制
发表时间：
1980
影响因子：
3.8
通讯作者：
S. Cohen
中科院分区：
文献类型：
--
作者：
C. P. Chen;V. T. Vu;S. Cohen
从成年雄性大鼠中制备分离的肝细胞，并在37 ℃下在含有痕量[14 C]利多卡因的Krebs碳酸氢盐缓冲液（pH 7.4）中孵育。在加入标记材料后2分钟内可证明利多卡因蓄积。延长潜伏期并没有导致组织与培养基（T M）比的增加。吸收不受降低的温度（27°C）的影响。在较宽的利多卡因浓度范围内，摄取没有饱和。代谢抑制剂不抑制利多卡因的摄取。薄层色谱法表明，一部分利多卡因在实验期间被代谢。凝胶渗透色谱法显示，大部分利多卡因与细胞成分可逆结合，而三分之一的放射性与大分子不可逆结合。这些结果表明利多卡因的肝脏吸收不是通过载体系统介导的;与肝脏成分的结合可能是观察到的累积的原因。此外，孵育培养基中加入dl-普萘洛尔导致利多卡因摄取浓度相关性降低，表明利多卡因和普萘洛尔之间可能存在临床重要相互作用。
Isolated hepatocytes were prepared from adult male rats and were incubated at 37°C in Krebs' bicarbonate buffer (pH 7.4) containing trace amounts of [14C]lidocaine. Accumulation of lidocaine was demonstrable within 2 min following the addition of the labeled material. Prolongation of the incubation period did not result in an increase in tissue to medium (T M ) ratio. The uptake was not affected by a reduced temperature (27°C). There was no saturation of uptake over a wide range of lidocaine concentration. Uptake of lidocaine was not inhibited by metabolic inhibitors. Thin-layer chromatography indicated that a portion of lidocaine was metabolized during the experimental period. Gel permeation chromatography showed that the majority of lidocaine was reversibly bound to cellular components, while one-third of the radioactivity was irreversibly associated with macromolecules. These results suggest that hepatic uptake of lidocaine is not mediated through a carrier system; binding to hepatic components may account for the observed accumulation. In addition, inclusion of dl-propranolol in the incubation medium caused a concentration-related decrease in lidocaine uptake and indicated a potential for clinically important interaction between lidocaine and propranolol.