Aldosterone metabolism in cultures of rat renal cortical and medullary cells.
The metabolism of 4-(14)C-d-aldosterone (at 3 nM) was studied in the primary target organ of the hormone, in renal cortical and medullary cell cultures obtained from Wistar rats. Larger amounts of aldosterone were metabolized in medullary cells than in cortical cells, as measured by a decreased 4-(14)C-d-aldosterone radioactivity concentration (26+/-9% and 12+/-7% of the initial aldosterone added, respectively (n=5, p<0.05)). The 14C radiometabolites of aldosterone in both cultures co-chromatographed with 5alpha dihydro- (DHA) and 3alpha,3beta tetrahydroaldosterone (THA). Aldosterone metabolism was totally inhibited by a mineralocorticoid receptor antagonist canrenoat (Soldactone) (at 10(-5) to 10(-3) M), while the glucocorticoid receptor antagonist RU 38486 (Roussel UCLAF) (at 10(-5) to 10(-4) M) had no effect. Thus, the study confirmed that, in rat kidney, aldosterone can be converted to its reduced metabolites by a metabolism which is inhibited by a mineralocorticoid receptor antagonist. This indicated that the metabolism might play some role in modulation of the intracellular response to aldosterone in the kidney.
Egfjord
M
M
Medical Department P, Rigshospitalet, Copenhagen, Denmark.
Dahl
H B
HB
Kayser
C
C
Blaehr
H
H
D000450:Aldosterone / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D002191:Canrenoic Acid / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007672:Kidney Cortex / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors
D002250:Carbon Radioisotopes; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D000450:Aldosterone; D002191:Canrenoic Acid