Akerboom T, Lenzen R, Schneider I, Sies H
Biochem Pharmacol. 1987 Sep 15;36(18):3037-42. doi: 10.1016/0006-2952(87)90221-8.
The calcium-ionophore A23187 causes a reversible increase of the hydrostatic pressure in the portal vein of perfused rat liver. Concomitantly, hepatic functions like the production of bile and the transhepatic movement of the bile acid taurocholate are diminished, mainly due to decreased uptake. These phenomena are partly explained by changes in the microcirculation of the liver, visualized by Trypan blue staining. Both the increase in portal pressure and the major part of the decrease of biliary excretion of taurocholate and bile flow are prevented by the addition of the vasodilator papaverine. The type I antiarrhythmic drugs quinidine and N-propylajmaline bitartrate (NPA), at high concentrations, also induce a rise in portal pressure and act as a cholestatic agent. The rise in portal pressure caused by NPA requires the presence of extracellular calcium and is counteracted by papaverine. In contrast to A23187, the cholestasis caused by NPA is not influenced by papaverine. While NPA decreases the hepatic uptake and biliary excretion of taurocholate, papavarine is able to restore only the uptake and not the excretion. The concentration of taurocholate in the bile is not significantly changed by NPA.
钙离子载体A23187可使灌注大鼠肝脏门静脉的流体静压可逆性升高。与此同时，诸如胆汁生成及胆汁酸牛磺胆酸盐的经肝转运等肝功能会减弱，这主要是由于摄取减少所致。这些现象部分可通过锥虫蓝染色观察到的肝脏微循环变化来解释。添加血管扩张剂罂粟碱可防止门静脉压力升高以及牛磺胆酸盐胆汁排泄和胆汁流量减少的主要部分。I类抗心律失常药物奎尼丁和酒石酸N - 丙基阿马林（NPA）在高浓度时也会导致门静脉压力升高，并起胆汁淤积剂的作用。NPA引起的门静脉压力升高需要细胞外钙的存在，且可被罂粟碱抵消。与A23187不同，NPA引起的胆汁淤积不受罂粟碱影响。虽然NPA会降低牛磺胆酸盐的肝脏摄取和胆汁排泄，但罂粟碱仅能恢复摄取，而不能恢复排泄。NPA不会使胆汁中牛磺胆酸盐的浓度发生显著变化。
