AJP - Renal Physiology, Vol 259, Issue 4 672-F678, Copyright © 1990 by American Physiological Society
Glucocorticoid receptors mediate mineralocorticoid-like effects in cultured collecting duct cells
A. Naray-Fejes-Toth and G. Fejes-Toth
Hypertension Research Division, Henry Ford Hospital, Detroit, Michigan 48202.
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).
