Corticosterone induces 11 beta-HSD and mineralocorticoid specificity in an amphibian urinary bladder cell line

Am J Physiol. 1993 Feb;264(2 Pt 1):C317-22. doi: 10.1152/ajpcell.1993.264.2.C317.

Abstract

We have examined the mineralocorticoid specificity in a TBM 18-23 cell line derived from the toad bladder epithelium. In cells grown on porous substrate, corticosterone was more potent than aldosterone in stimulating a sodium transport response, measured by the short-circuit current method 6 h after hormone addition [mean affinity constant (K0.5) for corticosterone = 1 nM vs. K0.5 for aldosterone = 8 nM]. The time course of effects and saturation kinetics were identical for both agonists, suggesting interaction with identical receptors. Whereas the dose-response relationship for aldosterone did not change with time of incubation (6 vs. 24 h), the dose-response curve for corticosterone became biphasic at 24-h incubation (apparent K0.5 as high as 40 nM), demonstrating that corticosterone became apparently less potent with time. Pretreatment with carbenoxolone, a potent inhibitor of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), restored full sensitivity at 24-h incubation to corticosterone. The 11 beta-HSD activity was low during the first 3 h of incubation in the presence of 3 nM corticosterone, and only a small fraction (approximately 7%) of corticosterone was metabolized. At 24-h incubation, 11 beta-HSD activity increased approximately 2.5-fold (P < 0.001, n = 8). We conclude that 11 beta-HSD activity is induced by its own substrate in TBM cells in parallel with the induction of the carbenoxolone-sensitive sodium transport response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenases
  • Aldosterone / pharmacology
  • Animals
  • Binding, Competitive
  • Biological Transport / drug effects
  • Bufo marinus
  • Carbenoxolone / metabolism
  • Carbenoxolone / pharmacology
  • Cell Line
  • Corticosterone / pharmacology*
  • Dose-Response Relationship, Drug
  • Epithelium / metabolism
  • Hydroxysteroid Dehydrogenases / metabolism*
  • Mineralocorticoids / metabolism*
  • Sodium / metabolism
  • Time Factors
  • Urinary Bladder / cytology
  • Urinary Bladder / metabolism*

Substances

  • Mineralocorticoids
  • Aldosterone
  • Sodium
  • Hydroxysteroid Dehydrogenases
  • 11-beta-Hydroxysteroid Dehydrogenases
  • Carbenoxolone
  • Corticosterone