氯丙嗪对分离的大鼠肝细胞中牛磺胆酸盐转运的影响。

Effects of chlorpromazine on taurocholate transport in isolated rat hepatocytes.

作者信息

Stacey N H

机构信息

National Institute of Occupational Health and Safety, University of Sydney, N.S.W., Australia.

出版信息

Biochem Pharmacol. 1988 Nov 1;37(21):4129-34. doi: 10.1016/0006-2952(88)90106-2.

DOI:10.1016/0006-2952(88)90106-2

PMID:3190752

Abstract

Chlorpromazine has been shown to have no effect on the uptake of the endogenous bile salt substrate, taurocholate, by isolated rat hepatocytes. It has been shown, however, to inhibit directly release of taurocholate from pre-loaded cells over extended incubation. However, there was no inhibition of the efflux process per se as shown by similar initial rates of taurocholate efflux in the presence or absence of chlorpromazine. Pretreatment of rats with chlorpromazine (100 mumoles/kg) resulted in no change in the ability to transport (that is, accumulate or secrete) taurocholate by hepatocytes isolated 2, 24, 36, 48, or 60 hr later. The data indicate that, if a direct effect on bile acid transport is important in chlorpromazine induced biliary dysfunction, then it involves release rather than uptake at the cell membrane. However, as efflux itself is not inhibited chlorpromazine may interfere with release of taurocholate from intracellular sites.

摘要

氯丙嗪已被证明对分离的大鼠肝细胞摄取内源性胆盐底物牛磺胆酸盐没有影响。然而，研究表明，在延长孵育时间的情况下，氯丙嗪可直接抑制预先加载细胞中牛磺胆酸盐的释放。然而，正如在有或没有氯丙嗪存在的情况下牛磺胆酸盐外流的初始速率相似所表明的那样，氯丙嗪本身对流出过程没有抑制作用。用氯丙嗪（100微摩尔/千克）预处理大鼠，在2、24、36、48或60小时后分离的肝细胞转运（即积累或分泌）牛磺胆酸盐的能力没有变化。数据表明，如果氯丙嗪诱导的胆汁功能障碍中对胆汁酸转运的直接作用很重要，那么它涉及细胞膜上的释放而非摄取。然而，由于外流本身未受抑制，氯丙嗪可能会干扰牛磺胆酸盐从细胞内位点的释放。