Velázquez H, Náray-Fejes-Tóth A, Silva T, Andújar E, Reilly R F, Desir G V, Ellison D H
VA Connecticut Healthcare System West Haven 06516, USA.
Kidney Int. 1998 Aug;54(2):464-72. doi: 10.1046/j.1523-1755.1998.00036.x.
Although the renal cortical collecting duct (CCD) is a principal target for aldosterone, recent evidence suggests that salt transport by other nephron segments may also be regulated by aldosterone. Electroneutral and thiazide-sensitive NaCl cotransport by the distal convoluted tubule (DCT) of the rat is increased in animals deprived of dietary NaCl. We tested the hypothesis that the DCT of the rabbit is an aldosterone target tissue.
The single-nephron reverse-transcriptase/polymerase chain reaction (RT-PCR) technique was used to determine mRNA expression of NaCl cotransporter and 11 beta-HSD 2 in dissected nephron segments. The rabbit NaCl cotransporter was first cloned and rabbit-specific primers selected. A micro-assay was developed to assess 11 beta-HSD 2 enzyme activity in 0.5 mm samples of the same nephron segments.
NaCl cotransporter was expressed in 0 of 6 proximal tubule (PT), 6 of 6 DCT and 3 of 6 CCD samples, while 11 beta-HSD was found in 0 of 7 PT, 7 of 7 DCT and 9 of 9 CCD samples. Corticosterone was converted to 11-dehydrocorticosterone at a high rate and to a similar extent by both the DCT and CCD, but not the PT.
We conclude that the DCT is a target tissue for the action of aldosterone. Axial heterogeneity of electroneutral (in DCT) and electrogenic (in CCD) Na transporters along the distal nephron may improve sodium recovery in low salt and volume states.
尽管肾皮质集合管(CCD)是醛固酮的主要作用靶点,但最近的证据表明,其他肾单位节段的盐转运也可能受醛固酮调节。在饮食中缺乏氯化钠的动物中,大鼠远曲小管(DCT)的电中性和噻嗪敏感型氯化钠共转运增加。我们检验了兔DCT是醛固酮作用靶点组织这一假说。
采用单肾单位逆转录酶/聚合酶链反应(RT-PCR)技术,测定分离的肾单位节段中氯化钠共转运体和11β-羟类固醇脱氢酶2(11β-HSD 2)的mRNA表达。首先克隆兔氯化钠共转运体并选择兔特异性引物。开发了一种微量测定法,以评估相同肾单位节段0.5毫米样本中的11β-HSD 2酶活性。
在6个近端小管(PT)样本中的0个、6个DCT样本中的6个以及6个CCD样本中的3个中检测到氯化钠共转运体表达,而在7个PT样本中的0个、7个DCT样本中的7个以及9个CCD样本中的9个中发现了11β-HSD。皮质酮在DCT和CCD中均以高速率且在相似程度上转化为11-脱氢皮质酮,但在PT中未发生转化。
我们得出结论,DCT是醛固酮作用的靶点组织。远曲小管中电中性(在DCT中)和生电性(在CCD中)钠转运体的轴向异质性可能会在低盐和低容量状态下改善钠的重吸收。