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醛固酮在离体肾小管中的结合II. 兔肾单位浓度依赖性的放射自显影研究

Aldosterone binding in isolated tubules II. An autoradiographic study of concentration dependency in the rabbit nephron.

作者信息

Farman N, Vandewalle A, Bonvalet J P

出版信息

Am J Physiol. 1982 Jan;242(1):F69-77. doi: 10.1152/ajprenal.1982.242.1.F69.

Abstract

Specific binding of aldosterone along the rabbit nephron was investigated using an autoradiographic method on microdissected tubules within a large range of [3H]aldosterone ([3H]A) concentrations (3 X 10(-10) to 2 X 10(-8) M). Paired incubations with [3H]A in the presence or absence of unlabeled A (100-fold excess) were done to determine the specific binding. In addition, competition studies (10 times excess) with A, dexamethasone (Dex), and estradiol (E) were performed. No specific nuclear binding was detected in the proximal convoluted tubule and pars recta. In the cortical collecting tubule (CCT), a high specific labeling occurred at concentrations of A as low as 3 X 10(-10) M that plateaued at 1.5 X 10(-9) M. Aldosterone was the best competitor. In the bright and granular distal tubule, the binding resembled that of CCT, but Dex was nearly as potent a competitor as A. All along the loop of Henle and in the medullary collecting duct, the binding of A was weak at low concentrations and gradually rose with concentration without reaching a plateau. An almost equivalent displacement was obtained by A and Dex in 10-fold excess. We conclude that aldosterone binds mostly to mineralocorticoid sites in the collecting tubule, whereas the binding appears to be to both mineralo- and glucocorticoid sites in the distal tubule, in the different parts of the loop of Henle, and in the medullary collecting tubule.

摘要

利用放射自显影法,在大范围的[3H]醛固酮([3H]A)浓度(3×10−10至2×10−8M)下,对显微解剖的兔肾小管进行研究,以探究醛固酮在兔肾单位中的特异性结合。在有或无未标记的A(100倍过量)存在的情况下,与[3H]A进行配对孵育,以确定特异性结合。此外,还进行了与A、地塞米松(Dex)和雌二醇(E)的竞争研究(10倍过量)。在近端曲管和直部未检测到特异性核结合。在皮质集合管(CCT)中,在低至3×10−10M的A浓度下出现高特异性标记,并在1.5×10−9M时达到平台期。醛固酮是最佳竞争者。在明亮和颗粒状的远曲小管中,结合情况与CCT相似,但Dex作为竞争者的效力几乎与A相同。在整个髓袢和髓质集合管中,低浓度时A的结合较弱,且随浓度逐渐升高但未达到平台期。10倍过量的A和Dex产生了几乎等效的置换。我们得出结论,醛固酮主要与集合管中的盐皮质激素位点结合,而在远曲小管、髓袢不同部位以及髓质集合管中,其结合似乎是与盐皮质激素和糖皮质激素位点均有关。

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