Hegner D, Kroker R, Anwer M S
Arzneimittelforschung. 1979;29(1):11-5.
Isolated perfused rat liver was used to characterize the choleretic action of 4-[4-chloro-N-(4-methoxyphenyl)-benzamido]-butyric acid (clanobutin). The dose-dependent increase of the bile flow was associated with an increase of the Na+ secretion. In in vitro studies the drug inhibited the Na+-K+-ATPase of the sinusoidal membrane more than that of the canalicular membrane in a dose-dependent manner. The following hypothesis was proposed to explain the choleretic action of clanobutin. The intracellular Na+ concentration increased due to the inhibition of the sinusoidal Na+-K+-ATPase. This is then compensated by transporting the extra Na+ into the bile. However, it cannot be ruled out that Na+ is transported as counterion during hepatobiliary transport of clanobutin or else its metabolites. The effect of the drug seems to be non-specific since other enzymes of the plasma membrane were also inhibited.
采用离体灌注大鼠肝脏来表征4-[4-氯-N-(4-甲氧基苯基)-苯甲酰胺基]-丁酸(氯诺布汀)的利胆作用。胆汁流量的剂量依赖性增加与Na⁺分泌增加相关。在体外研究中,该药物以剂量依赖性方式对肝血窦膜Na⁺-K⁺-ATP酶的抑制作用比对胆小管膜的抑制作用更强。提出了以下假设来解释氯诺布汀的利胆作用。由于肝血窦Na⁺-K⁺-ATP酶受到抑制,细胞内Na⁺浓度升高。然后通过将额外的Na⁺转运到胆汁中来进行补偿。然而,不能排除在氯诺布汀或其代谢产物的肝胆转运过程中,Na⁺作为抗衡离子被转运。该药物的作用似乎是非特异性的,因为质膜的其他酶也受到了抑制。