Steroid hormone stimulation of Na+ transport in A6 cells is mediated via glucocorticoid receptors

Am J Physiol. 1993 Apr;264(4 Pt 1):C875-84. doi: 10.1152/ajpcell.1993.264.4.C875.


The A6 cell line derived from the toad kidney forms polarized, highly differentiated epithelial monolayers in culture and has been utilized as an experimental model for studying regulation of transepithelial Na+ transport by aldosterone. In the present study we evaluated the specific role(s) of glucocorticoid and mineralocorticoid receptors in mediating this enhanced electrogenic Na+ transport, which was measured experimentally as an increase in short-circuit current (Isc). Our data demonstrate that specific glucocorticoid agonists (100 nM), including RU 28362 and RU 26988, elicit "mineralocorticoid-like" increases in Isc that are blocked by the glucocorticoid antagonist RU 38486 but are unaffected by mineralocorticoid antagonists including RU 28318 and RU 26752. The stimulatory effects of aldosterone (100 nM) were also blocked by RU 38486 and not by mineralocorticoid antagonists. These data extend earlier studies suggesting that in this cell line aldosterone mediates its physiological effects via binding with relatively low affinity (dissociation constant Kd congruent to 25-50 nM) to glucocorticoid receptors, despite the presence of apparently normal mineralocorticoid receptors. Our in vitro biochemical studies also demonstrate that A6 glucocorticoid receptor complexes can be thermally activated or transformed to DNA binding forms which exhibit altered elution profiles from anion-exchange resins. Thus, based on several criteria, these amphibian glucocorticoid receptors appear very similar to classical mammalian receptors and are capable of mediating all of the stimulatory effects of aldosterone on net Na+ transport.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androstanols / pharmacology
  • Animals
  • Biological Transport, Active / drug effects
  • Cell Line
  • DNA-Binding Proteins / physiology
  • Glucocorticoids / antagonists & inhibitors
  • Glucocorticoids / pharmacology*
  • Kidney
  • Kinetics
  • Mifepristone / pharmacology
  • Mineralocorticoids / pharmacology*
  • Nephrons
  • Receptors, Glucocorticoid / drug effects
  • Receptors, Glucocorticoid / isolation & purification
  • Receptors, Glucocorticoid / physiology*
  • Sodium / metabolism*
  • Structure-Activity Relationship
  • Triamcinolone Acetonide / metabolism
  • Xenopus laevis


  • Androstanols
  • DNA-Binding Proteins
  • Glucocorticoids
  • Mineralocorticoids
  • Receptors, Glucocorticoid
  • Mifepristone
  • RU 26988
  • 11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one
  • Sodium
  • Triamcinolone Acetonide