The "mineralocorticoid-like" actions conferred on corticosterone by carbenoxolone are inhibited by the mineralocorticoid receptor (type I) antagonist RU28318.
We have previously demonstrated, in adrenalectomized male rats, that the liquorice derivative carbenoxolone (CS) can confer mineralocorticoid (MC)-like activity upon the glucocorticoid corticosterone (B) and amplify the Na(+)-retaining actions of aldosterone (Aldo) and deoxycorticosterone (DOC). The purpose of the present study was to determine whether the MC-like effects of B and the amplified actions of ALDO and DOC in the presence of CS are mediated via the occupation of type I (MC) receptors. In adrenalectomized male rats, B (100 micrograms/rat) alone produced a significant kaliuresis, but no antinatriuresis. This kaliuresis was blocked by the type I (MC) receptor antagonist RU28318 (300 micrograms/rat). In the presence of CS (2.5 mg/rat), B produced a significant Na+ retention, and the kaliuretic activity of B was significantly enhanced. This CS-induced antinatriuresis produced by B was significantly reduced by RU28318, as was the amplified kaliuresis. The MC effects of either Aldo (0.05 micrograms/rat) or DOC (5 micrograms/rat) alone were, as expected, reduced by RU28318 (300 micrograms/rat). As previously reported, CS amplified only the Na(+)-retaining actions of Aldo and DOC, and it was also possible to reduce these amplified effects with RU28318. The present study demonstrates that in the presence of CS, the MC actions of B, Aldo, and DOC are mediated to a large extent via the occupation of type I (MC) receptors.
Souness
G W
GW
Department of Pathology and Laboratory Medicine, Miriam Hospital, Rhode Island 02906.
Morris
D J
DJ
D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology*; D003345:Corticosterone / Q000494:pharmacology*; D003404:Creatinine / Q000652:urine; D003900:Desoxycorticosterone / Q000494:pharmacology; D008297:Male; D008901:Mineralocorticoids / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000652:urine; D051381:Rats; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology
D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D013148:Spironolactone; D003900:Desoxycorticosterone; D000450:Aldosterone; C041006:RU 28318; D003404:Creatinine; D002229:Carbenoxolone; D011188:Potassium; D003345:Corticosterone