Hashimoto N, Maruyama T, Toda G, Ikeda Y, Sugiyama Y, Oka H
Gastroenterol Jpn. 1987 Apr;22(2):194-202. doi: 10.1007/BF02774217.
In the isolated perfused rat liver, the effects of calmodulin (CaM) antagonists, chlorpromazine (CPZ), trifluoperazine (TFP), W-7 and W-5, on secretion of bile and bile acid were compared. Without addition of taurocholic acid to the perfusate, TFP (200 microM or higher), CPZ (200 microM) and W-7 (400 microM) decreased the bile flow transiently. In contrast, W-5 did not decrease the bile flow. Taking into consideration the binding of TFP and CPZ to bovine serum albumin in the perfusate, they diminished the bile flow by inhibiting CaM function. This was also supported by the difference between the effects of W-7 and W-5. These findings suggested that CaM was involved in the secretion of bile. Under the constant infusion of taurocholic acid into the perfusate, CaM antagonists decreased the secretion of bile acid. However this might be due to the inhibition of bile acid uptake, because these agents inhibited the uptake into isolated rat hepatocytes. The concentrations required for inhibition of the uptake were near to those which decreased the viability, suggesting that the inhibition was due to their non-specific cytotoxic effect. Future studies must be carried out to determine whether CaM is involved in the secretion of bile acid.
在离体灌注大鼠肝脏中，比较了钙调蛋白（CaM）拮抗剂氯丙嗪（CPZ）、三氟拉嗪（TFP）、W-7和W-5对胆汁和胆汁酸分泌的影响。在灌注液中不添加牛磺胆酸的情况下，TFP（200微摩尔或更高）、CPZ（200微摩尔）和W-7（400微摩尔）可使胆汁流量短暂降低。相比之下，W-5并未降低胆汁流量。考虑到TFP和CPZ与灌注液中牛血清白蛋白的结合，它们通过抑制CaM功能而减少了胆汁流量。W-7和W-5作用效果的差异也支持了这一点。这些发现表明CaM参与了胆汁的分泌。在向灌注液中持续输注牛磺胆酸的情况下，CaM拮抗剂可降低胆汁酸的分泌。然而，这可能是由于胆汁酸摄取受到抑制，因为这些药物抑制了胆汁酸进入分离的大鼠肝细胞。抑制摄取所需的浓度接近于降低细胞活力的浓度，这表明这种抑制是由于它们的非特异性细胞毒性作用。必须开展进一步研究以确定CaM是否参与胆汁酸的分泌。
