Corticosterone increases Na(+)-K(+)-ATPase activity in rat cortical collecting ducts with inhibition of 11 beta-hydroxysteroid dehydrogenase.
To examine a physiological role of 11 beta-hydroxysteroid dehydrogenase (11OHSD) in the aldosterone target tissue, 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(-6) M) and the plasma carbenoxolone concentration was about 10(-7) M. Furthermore, the direct effect of carbenoxolone was examined in the microdissected CCD 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(-6) M, 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.
Tsuganezawa
H
H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Hayashi
M
M
Fujii
Y
Y
Yamaji
Y
Y
Iyori
M
M
Saruta
T
T
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000315:Adrenalectomy; D000450:Aldosterone / Q000097:blood; D000818:Animals; D002229:Carbenoxolone / Q000097:blood / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000502:physiology*; D066298:In Vitro Techniques; D007685:Kidney Tubules, Collecting / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar / Q000601:surgery; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D000450:Aldosterone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D000254:Sodium-Potassium-Exchanging ATPase; D002229:Carbenoxolone; D003345:Corticosterone