Hamlin S, Rahman K, Carrella M, Coleman R
Department of Biochemistry, University of Birmingham, U.K.
Biochem J. 1990 Feb 1;265(3):879-85. doi: 10.1042/bj2650879.
Exposure of isolated perfused rat livers to either 100 microM-forskolin, a potent activator of adenylate cyclase, or to 0.5 mM-concentrations of the cAMP analogues chlorophenylthio cAMP (CPTcAMP), dibutyryl cAMP (dbcAMP) and 8-bromo cAMP (8BrcAMP), to provoke increases in intracellular concentrations of cAMP, resulted in marked changes in bile volume and composition. Bile flow reached a peak after 10 min, before declining towards control levels, and an increase in several secretory parameters was also observed at this time. At 20 min, a substantial decrease in the output of both phospholipid and cholesterol was evident, and this suppression of secretion was maintained throughout the remainder of the experiment. The order of effectiveness of the cAMP-elevating agents at decreasing biliary lipid output was CPTcAMP greater than forskolin greater than dbcAMP greater than 8BrcAMP. Biliary output of bile acids was essentially unaltered compared with controls; similarly, no decrease in the secretion of protein and triacylglycerols into the perfusion medium was observed. This suggests that the elevation of intracellular levels of cAMP may cause a selective inhibition of biliary lipid output rather than a more general inhibition of hepatic secretion.
将离体灌注的大鼠肝脏暴露于100微摩尔的福斯高林（一种有效的腺苷酸环化酶激活剂）或0.5毫摩尔浓度的环磷酸腺苷类似物氯苯硫代环磷酸腺苷（CPTcAMP）、二丁酰环磷酸腺苷（dbcAMP）和8-溴环磷酸腺苷（8BrcAMP）中，以促使细胞内环磷酸腺苷浓度升高，结果导致胆汁体积和成分发生显著变化。胆汁流量在10分钟后达到峰值，随后降至对照水平，此时还观察到几个分泌参数增加。在20分钟时，磷脂和胆固醇的输出量明显大幅下降，并且在实验的剩余时间内这种分泌抑制一直保持。在降低胆汁脂质输出方面，环磷酸腺苷升高剂的有效性顺序为CPTcAMP＞福斯高林＞dbcAMP＞8BrcAMP。与对照相比，胆汁酸的胆汁输出基本未改变；同样，未观察到灌注介质中蛋白质和三酰甘油的分泌减少。这表明细胞内环磷酸腺苷水平的升高可能导致胆汁脂质输出的选择性抑制，而不是对肝脏分泌的更普遍抑制。
