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Na + ‐Cl ‐ Cotransporter (NCC) is Differentially Regulated by Aldosterone in Early and late Distal Convoluted Tubule
Author(s) -
Poulsen Søren,
Christensen Birgitte
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb733
Subject(s) - distal convoluted tubule , aldosterone , cotransporter , endocrinology , medicine , chemistry , blot , mineralocorticoid , biology , kidney , sodium , biochemistry , nephron , gene , organic chemistry
The Na + ‐Cl ‐ cotransporter (NCC) is expressed in renal distal convoluted tubule (DCT)1 and DCT2. Inherited NCC mutations lead to Gitelmans syndrome causing Na + and K + disturbances. NCC is stimulated by aldosterone, which is believed to depend upon the enzyme 11B‐hydroxysteroid dehydrogenase type 2 (11BHSD2). Because 11BHSD2 is expressed in DCT2 and not DCT1, it is widely believed that aldosterone stimulates NCC primarily in DCT2. However, the conjecture has to date not been directly tested. Hence, we hypothesized that the abundances of total NCC and NCC phosphorylated at T58 (pT58‐NCC; the phosphorylation increases NCC Na + transport capacity) were stimulated by aldosterone in DCT2 but not in DCT1. B6/C57 male mice were administrated 100 µg aldosterone kg/24 h for 6 days. Western blotting confirmed that aldosterone stimulated total NCC and pT58‐NCC (P < 0.001). DCT1‐specific semi‐quantitative confocal fluorescence microscopy detected no effect of aldosterone on NCC and p58‐NCC abundances (P > 0.05). By contrast, NCC and pT58‐NCC were clearly stimulated in DCT2 and at the junction between DCT2 and CNT (P < 0.01). Collectively, our data suggest that aldosterone stimulates NCC and pT58‐NCC abundances in DCT2, whereas aldosterone has no/a minimal effect in DCT1. The data are consistent with what was previously suggested. Financial support was provided by MEMBRANES, Aarhus University, Denmark.