Down-regulation of the mineralocorticoid receptor by dexamethasone in an amphibian kidney cell line (A6).
The A6 cell line, derived from Xenopus kidney, is an in vitro model of cortico-steroid mediated transepitheial Na+ transport stimulation. We report the apparent down-regulation of mineralocorticoid receptor levels in A6 cells, in response to the presence of the synthetic glucorticoid dexamethasone in the culture medium. Mineralocorticoid receptor binding was suppressed to approximately 25% of control following 24-hour exposure to 10nM dexamethasone. Scatchard analysis of concentration-binding experiments show down-regulation of maximum binding capacity by Dex exposure with no alteration of MR affinity, i.e., alteration of MR number only. The effect is dose-responsive with half-maximal down regulation at 1nM. Maximal inhibition of binding occurred after 24-hours exposure to dexamethasone. The inhibitory effect of dexamethasone on MR binding was unique for the glucocorticoid, with no effect exhibited following similar treatment with an androgen, an estrogen, or a mineralocorticoid.
Hagley
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RD
Department of Internal Medicine, Medical College of Virginia/VCU, Richmond 23219-0145, USA.
Watlington
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CO
D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004848:Epithelium / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000378:metabolism*; D013379:Substrate Specificity; D013997:Time Factors; D014981:Xenopus
D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D003907:Dexamethasone