Corticosterone induces 11 beta-HSD and mineralocorticoid specificity in an amphibian urinary bladder cell line.
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.
Gaeggeler
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HP
Institut de Pharmacologie et de Toxicologie de l'Université, Lausanne, Switzerland.
Duperrex
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H
Hautier
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Rossier
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BC
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D002024:Bufo marinus; D002229:Carbenoxolone / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D003345:Corticosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D008901:Mineralocorticoids / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013997:Time Factors; D001743:Urinary Bladder / Q000166:cytology / Q000378:metabolism*
D008901:Mineralocorticoids; D000450:Aldosterone; D012964:Sodium; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D002229:Carbenoxolone; D003345:Corticosterone