Glucocorticoid receptors mediate mineralocorticoid-like effects in cultured collecting duct cells.
To investigate the direct epithelial effects of corticosteroids on renal ion transport, we studied the influence of the pure glucocorticoid agonist RU 28362 and aldosterone on Na+ and K+ transport in primary cultures of immunodissected rabbit cortical collecting duct (CCD) cells. When grown on permeable supports in a steroid-free medium, CCD monolayers exhibited a lumen-negative transepithelial potential difference (PD) of 5.2 +/- 1.07 mV and a short-circuit current (SCC) of 8.54 +/- 2.2 microA/cm2. Transepithelial resistance averaged 660 +/- 49 omega/cm2. The cultures actively reabsorbed Na+ and secreted K+. Both aldosterone and RU 28362 significantly increased PD and SCC; the effects were time and dose dependent. The effect of RU 28362 was completely prevented by the glucocorticoid receptor antagonist RU 486, whereas ZK 91587, a specific mineralocorticoid receptor antagonist, did not block its effect. Both aldosterone and RU 28362 increased the bath-to-lumen concentration ratio of Na+ while lowering that of K+, indicating an increased Na+ reabsorption and K+ secretion. The number of Na(+)-K(+)-ATPase units was significantly enhanced (approximately 2-fold) by both RU 28362 and aldosterone. These results demonstrate that, in cultured CCD cells, not only aldosterone but also a pure glucocorticoid is able to exert mineralocorticoid-like effects, and this latter effect is mediated by glucocorticoid receptors. Because all parameters studied responded similarly to aldosterone and RU 28362, we speculate that in CCD cells glucocorticoids and mineralocorticoids might act by regulating the same gene(s).
Náray-Fejes-Tóth
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Hypertension Research Division, Henry Ford Hospital, Detroit, Michigan 48202.
Fejes-Tóth
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D000450:Aldosterone / Q000494:pharmacology; D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008901:Mineralocorticoids / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism
D000732:Androstanols; D008901:Mineralocorticoids; D011965:Receptors, Glucocorticoid; D000450:Aldosterone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D012964:Sodium; D011188:Potassium