Sandle G I, McGlone F
Gut. 1987 Jun;28(6):701-6. doi: 10.1136/gut.28.6.701.
Single pharmacological doses of glucocorticoid hormones stimulate net Na+ and water absorption, K+ secretion and electrical potential difference in rat distal colon and human rectum after five hours. To determine the cellular basis of these effects, the Na+ and K+ transport properties of epithelial cell membranes in rat distal colon were studied in vitro five hours after in vivo treatment with dexamethasone 600 micrograms/100 g body weight. Compared with control tissues, dexamethasone increased transepithelial voltage 3.5-fold (p less than 0.001) and short circuit current 4.5-fold (p less than 0.001), and decreased total resistance by 20% (p less than 0.005). Measurements of cell membrane voltages obtained with intracellular microelectrodes indicated that the dexamethasone-induced rise in transepithelial voltage reflected a significant decrease (p less than 0.05) in apical membrane voltage, consistent with the induction of apical Na+ channels and the stimulation of electrogenic Na+ absorption. Apical addition of 10(-4) mol/l amiloride (a Na+ channel blocker) and then 30 mmol/l tetraethylammonium chloride (TEA; a K+ channel blocker) to control tissues had little or no effect on transepithelial electrical parameters, indicating the absence of significant apical Na+ and K+ conductances. In contrast, in dexamethasone treated tissues, amiloride and TEA produced electrical changes that were consistent with the inhibition of glucocorticoid-induced apical Na+ and K+ conductances. Kinetic studies of the basolateral membrane Na+-K+ pump revealed that five hours after administration, dexamethasone had no effect on the maximum capacity of the pump for Na+ transport, but significantly increased the affinity of the pump for Na+, and the number of Na+ ions binding to each pump site. Thus, the acute stimulatory effects of dexamethasone on distal colonic Na+ absorption and K+ secretion reflect increased apical membrane conductance to Na+ and K+, and an increase in the 'efficiency' of the basolateral membrane Na+-K+ pump.
单剂量糖皮质激素在五小时后可刺激大鼠远端结肠和人类直肠的净钠和水吸收、钾分泌以及电位差。为确定这些效应的细胞基础，在用600微克/100克体重的地塞米松进行体内治疗五小时后，对大鼠远端结肠上皮细胞膜的钠和钾转运特性进行了体外研究。与对照组织相比，地塞米松使跨上皮电压增加了3.5倍（p<0.001），短路电流增加了4.5倍（p<0.001），总电阻降低了20%（p<0.005）。用细胞内微电极测量细胞膜电压表明，地塞米松诱导的跨上皮电压升高反映了顶端膜电压的显著降低（p<0.05），这与顶端钠通道的诱导和电生性钠吸收的刺激一致。向对照组织顶端加入10(-4)摩尔/升氨氯地平（一种钠通道阻滞剂），然后加入30毫摩尔/升四乙铵氯化物（TEA；一种钾通道阻滞剂），对跨上皮电参数几乎没有影响，表明不存在显著的顶端钠和钾电导。相反，在地塞米松处理的组织中，氨氯地平和TEA产生的电变化与糖皮质激素诱导的顶端钠和钾电导的抑制一致。基底外侧膜钠钾泵的动力学研究表明，给药五小时后，地塞米松对泵的钠转运最大能力没有影响，但显著增加了泵对钠的亲和力以及与每个泵位点结合的钠离子数量。因此，地塞米松对远端结肠钠吸收和钾分泌的急性刺激作用反映了顶端膜对钠和钾的电导增加，以及基底外侧膜钠钾泵“效率”的提高。
