Anwer M S
Am J Physiol. 1987 Mar;252(3 Pt 1):G357-64. doi: 10.1152/ajpgi.1987.252.3.G357.
The role of inorganic ions in hepatic transport and choleretic effect of ouabain was studied in isolated perfused rat liver to verify whether Na+-coupled ouabain uptake into hepatocytes is responsible for the choleretic effect. Hepatic uptake and clearance of ouabain were not significantly affected when perfusate Na+ was replaced by Li+ or choline+, chloride by nitrate or isethionate, or bicarbonate by tricine. However, these ion substitutions, with the exception of Li+, significantly reduced ouabain-induced choleresis and biliary electrolyte excretion. When ouabain was infused at different rates followed by perfusion without ouabain, changes in bile flow paralleled biliary excretion of ouabain rather than hepatic uptake. These results indicate that hepatic uptake of ouabain is not Na+ dependent and that the osmotic effect of biliary excreted ouabain is responsible for its choleretic effect. A part of the choleretic effect (30%) must also involve other mechanisms, since a permeable anion-like nitrate failed to substitute for perfusate chloride. Results of infusion studies also showed that ouabain was concentrated in liver (liver/perfusate = 30) and in bile (bile/liver = 15), indicating that ouabain is transported against its concentration gradient across both sinusoidal and canalicular membranes.
在离体灌注大鼠肝脏中研究了无机离子在哇巴因肝转运及利胆作用中的角色，以验证Na⁺偶联的哇巴因摄取进入肝细胞是否是利胆作用的原因。当用Li⁺或胆碱⁺替代灌注液中的Na⁺、用硝酸盐或羟乙磺酸盐替代氯化物、或用三羟甲基氨基甲烷替代碳酸氢盐时，哇巴因的肝摄取和清除率未受到显著影响。然而，除Li⁺外，这些离子替代显著降低了哇巴因诱导的胆汁分泌和胆汁电解质排泄。当以不同速率输注哇巴因后再进行无哇巴因灌注时，胆汁流量的变化与哇巴因的胆汁排泄平行，而非与肝摄取平行。这些结果表明，哇巴因的肝摄取不依赖于Na⁺，且胆汁中排泄的哇巴因的渗透作用是其利胆作用的原因。由于可渗透的阴离子如硝酸盐不能替代灌注液中的氯化物，所以一部分利胆作用（30%）必定还涉及其他机制。输注研究结果还表明，哇巴因在肝脏中浓缩（肝/灌注液 = 30）且在胆汁中浓缩（胆汁/肝脏 = 15），这表明哇巴因是逆其浓度梯度跨窦状隙和胆小管膜转运的。
