Paradoxical effects of mineralocorticoids on the ion gated sodium channel in embryologically diverse cells.
PCR analysis and Western blotting revealed the expression of the mineralocorticoid receptor (MCR) and the epithelial sodium channel (ENaC) genes at the level of RNA, DNA, and protein in several leukemic cell lines, fibroblasts from human cornea, and epithelial cells from ocular tissues. Following immunofluorescence, the MCR appeared to be primarily nuclear whereas the ENaC was almost exclusively membrane-bound. Paradoxically, the MCR-specific antagonist ZK 91587 actually stimulated the multiplication of human erythroblastic leukemia cells, contrary to the inhibitory effect of the antagonist RU 26752 on the multiplication of corneal fibroblasts; both effects were opposed by aldosterone. In quantitative PCR, both basal and aldosterone-induced levels of ENaC were diminished by ZK 91587 in the corneal fibroblast, in contrast to the stimulation observed in the retinal pigmentary epithelium. Thus, contrary to the existing notions, (a) antimineralocorticoids can act both as agonists and antagonists, and (b) the receptor-mediated action of mineralocorticoids on the sodium channel is not restricted to the epithelial cell.
Mirshahi
M
M
Inserm U 9912, Centre Universitaire des Cordeliers, Paris, France.
Golestaneh
N
N
Valamanesh
F
F
Agarwal
M K
MK
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004622:Embryo, Mammalian; D053503:Epithelial Sodium Channels; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D004915:Leukemia, Erythroblastic, Acute; D000451:Mineralocorticoid Receptor Antagonists; D008901:Mineralocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D053503:Epithelial Sodium Channels; D000451:Mineralocorticoid Receptor Antagonists; D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D015222:Sodium Channels; D013148:Spironolactone; D000450:Aldosterone; C047175:7-propyl spirolactone; C054537:ZK 91587