Baum M, Moe O W, Gentry D L, Alpern R J
Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas.
Am J Physiol. 1994 Sep;267(3 Pt 2):F437-42. doi: 10.1152/ajprenal.1994.267.3.F437.
Glucocorticoids play an important role in modulating proximal tubule acidification. Chronic systemic administration of dexamethasone increases the rate of bicarbonate absorption in isolated perfused proximal convoluted tubules and Na+/H+ antiporter activity in renal brush-border membrane vesicles. The proximal tubule expresses mRNA corresponding to two known Na+/H+ antiporter isoforms: NHE-3, an amiloride-resistant apical membrane Na+/H+ antiporter; and NHE-1, an amiloride-sensitive Na+/H+ antiporter found on most mammalian cells. Administration of dexamethasone for 1 and 2 days (600 micrograms/kg twice daily and 2 h before animals were killed) increased NHE-3 mRNA abundance 1.3- and 2.5-fold, respectively, but had no effect on NHE-1 mRNA abundance. Aminoglutethimide-induced glucocorticoid deficiency had no effect on NHE-1 or NHE-3 mRNA abundance. Incubation of proximal tubules for 3 h with 10(-5) M dexamethasone increased proximal tubule Na+/H+ antiporter activity from 0.69 +/- 0.04 to 0.92 +/- 0.03 pH units/min (P < 0.01); however, there was no increase in NHE-3 or NHE-1 mRNA abundance. Similarly, there was no effect on NHE-3 or NHE-1 mRNA abundance in rabbit renal cortex 4 h after intravenous administration of 600 micrograms/kg dexamethasone. Thus chronic dexamethasone increases NHE-3 but not NHE-1 mRNA abundance. The acute increase in Na+/H+ antiporter activity induced by dexamethasone occurs by mechanisms independent of changes in NHE-1 and NHE-3 mRNA abundance.
糖皮质激素在调节近端小管酸化过程中发挥着重要作用。长期全身性给予地塞米松可提高离体灌注近端曲管中碳酸氢盐的吸收速率以及肾刷状缘膜囊泡中钠氢交换体（Na⁺/H⁺ antiporter）的活性。近端小管表达与两种已知钠氢交换体亚型相对应的信使核糖核酸（mRNA）：NHE - 3，一种对阿米洛利耐药的顶端膜钠氢交换体；以及NHE - 1，一种在大多数哺乳动物细胞中发现的对阿米洛利敏感的钠氢交换体。给予地塞米松1天和2天（每天两次，每次600微克/千克，在处死动物前2小时给药）分别使NHE - 3 mRNA丰度增加了1.3倍和2.5倍，但对NHE - 1 mRNA丰度没有影响。氨基导眠能诱导的糖皮质激素缺乏对NHE - 1或NHE - 3 mRNA丰度没有影响。用10⁻⁵ M地塞米松孵育近端小管3小时，使近端小管钠氢交换体活性从0.69±0.04增加到0.92±0.03 pH单位/分钟（P<0.01）；然而，NHE - 3或NHE - 1 mRNA丰度没有增加。同样，静脉注射600微克/千克地塞米松4小时后，兔肾皮质中NHE - 3或NHE - 1 mRNA丰度也没有受到影响。因此，长期使用地塞米松可增加NHE - 3而非NHE - 1的mRNA丰度。地塞米松诱导的钠氢交换体活性急性增加是通过独立于NHE - 1和NHE - 3 mRNA丰度变化的机制发生的。
