Corticosterone increases Na⁺-K⁺-ATPase activity in rat cortisal collecting ducts with inhibition of 11β-hydroxysteroid dehydrogenase

To examine a physiological role of 11β-hydroxysteroid dehydrogenase (11OHSD) in the aldosterone target tissues, we measured Na⁺-K⁺-ATPase activity in the cortical collecting ducts (CCD) from adrenalectomized rats, which were treated with a physiological dose of corticosterone and/or carbenoxolone (an inhibitor of 11OHSD). The Na⁺-K⁺-ATPase activity in adrenalectomized rats was not significantly changed by either corticosterone alone or carbenoxolone alone, whereas its activity showed a significant increase only in the rats that received both corticosterone and carbenoxolone. In these rats, the plasma concentration of corticosterone was within the physiological range (10^-6M) and the plasma carbenoxolone concentration was about 10^-7M. Furthermore, the direct effect of carbenosolone was examined in the microdissected CCB because it has been reported that carbenoxolone per se had an affinity for the aldosterone receptor. Na⁺K⁺-ATPase activity in the microdissected CCD was increased in a dose-dependent manner after a 3-hour incubation with carbenoxolone, and this effect was completely inhibited by canrenoic acid (an aldosterone antagonist), However, the minimal carbenoxolone concentration exerting a stimulatory effect was 10^-6M, which is about 10 times higher than the plasma concentration of carbenoxolone in the in vivo treated rats. These results indicate that an inhibition of 11OHSD but not a direct action of carbenoxolone induces an increase in Na⁺-K⁺-ATPase activity, which is a well-known aldosterone effect in the CCD.