Simon F R, Sutherland E, Sutherland J
University of Colorado School of Medicine, Division of Gastroenterology, Denver.
Am J Physiol. 1988 May;254(5 Pt 1):G761-7. doi: 10.1152/ajpgi.1988.254.5.G761.
Sodium-potassium adenosinetriphosphatase (Na+-K+-ATPase) is modulated by functional demands. We determine whether Na+-K+-ATPase specific activity was changed by oral administration of different bile salts and whether upregulation in the liver is due to increased numbers of catalytic units. In rats after bile duct drainage for 18 h, Na+-K+-ATPase activity was reduced to 50% of control in liver and ileum but unchanged in jejunum and kidney. Increased Na+-K+-ATPase activity after short-term feeding of bile salts was noted only following trihydroxy bile salts, i.e., taurocholate (100 mg/100 g body wt) increased hepatic Na+-K+-ATPase 143% and ileum 138% above control, whereas jejunum and kidney were unchanged. Chronic feeding of trihydroxy bile salts for 4 days increased hepatic Na+-K+-ATPase (214-260%) and alkaline phosphatase (189-274%), whereas 5'-nucleotidase and Mg2+-ATPase activities were unchanged from control. Plasma membrane Na+-K+-ATPase activity significantly increased as early as 4 h after taurocholate administration, whereas homogenate activity did not rise until 16 h; both reached a new steady state between 24 and 48 h. Sixteen hours after bile salt feeding, increased Na+-K+-ATPase activity was blocked by cycloheximide, and in the liver increased enzyme activity (179%) was associated with a comparable change in sodium-dependent [gamma-32P]ATP binding (162%) to liver plasma membrane fractions. These studies show Na+-K+-ATPase activity adapts selectively in liver and ileum following administration of trihydroxy bile salts, and the process involves increased density of Na+-K+ pump sites on the liver plasma membrane.
钠钾腺苷三磷酸酶（Na⁺-K⁺-ATP酶）受功能需求的调节。我们确定口服不同胆汁盐是否会改变Na⁺-K⁺-ATP酶的比活性，以及肝脏中的上调是否归因于催化单位数量的增加。在胆管引流18小时后的大鼠中，肝脏和回肠中的Na⁺-K⁺-ATP酶活性降至对照的50%，但空肠和肾脏中的活性未改变。仅在喂食三羟基胆汁盐后，才观察到短期喂食胆汁盐后Na⁺-K⁺-ATP酶活性增加，即牛磺胆酸盐（100毫克/100克体重）使肝脏Na⁺-K⁺-ATP酶比对照增加143%，回肠增加138%，而空肠和肾脏未改变。连续4天喂食三羟基胆汁盐会使肝脏Na⁺-K⁺-ATP酶（增加214 - 260%）和碱性磷酸酶（增加1,89 - 274%）增加，而5'-核苷酸酶和Mg²⁺-ATP酶活性与对照相比未改变。早在给予牛磺胆酸盐4小时后，质膜Na⁺-K⁺-ATP酶活性就显著增加，而匀浆活性直到16小时才升高；两者在24至48小时之间达到新的稳态。喂食胆汁盐16小时后，环己酰亚胺可阻断Na⁺-K⁺-ATP酶活性的增加，并且在肝脏中，酶活性增加（179%）与肝质膜组分中钠依赖性[γ-³²P]ATP结合的类似变化（162%）相关。这些研究表明，给予三羟基胆汁盐后，肝脏和回肠中的Na⁺-K⁺-ATP酶活性会选择性适应，并且该过程涉及肝质膜上Na⁺-K⁺泵位点密度的增加。
