Laplace J R, Husted R F, Stokes J B
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
J Clin Invest. 1992 Oct;90(4):1370-8. doi: 10.1172/JCI116003.
It has recently been discovered that both mineralocorticoid (MC) and glucocorticoid (GC) hormones can stimulate electrogenic Na+ absorption by mammalian collecting duct cells in culture. In primary cultures of rat inner medullary collecting duct (IMCD) cells, 24-h incubation with either MC or GC agonist stimulates Na+ transport approximately threefold. We have now determined that the effects were not additive, but the time courses were different. As aldosterone is known to stimulate citrate synthase, Na+/K+ ATPase activity, and ouabain binding in cortical collecting duct principal cells, we determined the effects of steroids on these parameters in IMCD cells. MC and GC agonists both produced a small increase in citrate synthase activity. There was no increase in Na+/K+ ATPase activity but specific ouabain binding was increased more than two-fold by either agonist. To determine the role of apical Na+ entry in the steroid-induced effects, the Na+ channel inhibitor, benzamil, was used. Benzamil did not alter the stimulation of citrate synthase activity by either steroid. In contrast, GC stimulation of ouabain binding was prevented by benzamil, whereas MC stimulation was not. We conclude that there are differences in the way that MC and GC hormones produce an increased Na+ transport. Both appear to produce translocation (or activation) of pumps into the basolateral membrane. GC stimulation of pump translocation requires increased Na+ entry whereas MC stimulation does not.
最近发现,盐皮质激素(MC)和糖皮质激素(GC)均可刺激培养的哺乳动物集合管细胞进行电生性Na⁺吸收。在大鼠髓质内集合管(IMCD)细胞的原代培养中,用MC或GC激动剂孵育24小时可使Na⁺转运增加约三倍。我们现已确定,这些作用并非相加性的,但时间进程有所不同。由于已知醛固酮可刺激皮质集合管主细胞中的柠檬酸合酶、Na⁺/K⁺ATP酶活性和哇巴因结合,我们测定了类固醇对IMCD细胞中这些参数的影响。MC和GC激动剂均使柠檬酸合酶活性略有增加。Na⁺/K⁺ATP酶活性没有增加,但两种激动剂均可使特异性哇巴因结合增加两倍以上。为了确定顶端Na⁺进入在类固醇诱导作用中的作用,使用了Na⁺通道抑制剂苯甲咪。苯甲咪不会改变两种类固醇对柠檬酸合酶活性的刺激作用。相反,苯甲咪可阻止GC对哇巴因结合的刺激作用,而对MC的刺激作用则无影响。我们得出结论,MC和GC激素增加Na⁺转运的方式存在差异。两者似乎都能使泵转位(或激活)至基底外侧膜。GC对泵转位的刺激作用需要增加Na⁺进入,而MC的刺激作用则不需要。