Regulation of expression of the lung amiloride-sensitive Na+ channel by steroid hormones.
Molecular cloning of the amiloride-sensitive Na+ channel has permitted analysis of the mechanisms of its stimulation by steroids. In rat lung cells in primary culture, where its mRNA has been detected, the activity of an amiloride-sensitive channel, highly selective for Na+, is controlled by corticosteroids. Dexamethasone (0.1 microM) or aldosterone (1 microM) induced, after a minimum 10 h treatment, a large increase of the amiloride-induced hyperpolarization and of the amiloride-sensitive current. A parallel increase in the amount of the mRNA was observed. The corresponding gene is thus a target for steroid action. Using synthetic specific agonists and antagonists for mineralo- and glucocorticoid receptors, it has been shown that the steroid action on Na+ channel expression is mediated via glucocorticoid receptors. Triiodothyronine, known to modulate steroid action in several tissues, had no effect on both the amiloride-sensitive Na+ current and the level of the mRNA for the Na+ channel protein, but potentiates the stimulatory effect of dexamethasone. The increase in Na+ channel activity observed in the lung around birth can thus be explained by a direct increase in transcription of the Na+ channel gene.
Champigny
G
G
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
Voilley
N
N
Lingueglia
E
E
Friend
V
V
Barbry
P
P
Lazdunski
M
M
D000450:Aldosterone / Q000494:pharmacology*; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000451:Mineralocorticoid Receptor Antagonists; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism
D000451:Mineralocorticoid Receptor Antagonists; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D015222:Sodium Channels; D000450:Aldosterone; D000584:Amiloride; D003907:Dexamethasone