Tritiated 9alpha-fluorocortisol metabolism and binding in rat kidney.
Metabolism of 9alpha-fluorocortisol (9alpha-F) has been studied in rat kidney slices, homogenate, and in the isolated perfused kidney. These studies show that the rate of 9alpha-F metabolism varies depending upon the experimental conditions. The major metabolite formed, identified by mass spectrometry, is 20(xi)-dihydro-9alpha-fluorocortisol. The kidney slice experiments show that only 3H-9alpha-F and none of the metabolites bind to cytosolic receptors. In competition experiments performed with tritiated and unlabeled 9alpha-fluorocortisol, aldosterone (A), dexamethasone (DM) and triamcinolone acetonide (TA), 9alpha-F was found to bind to mineralocorticoid receptors with a lower affinity than A but also to glucocorticoid receptors with a higher affinity than A. The Scatchard plot analysis indicated that 3H-9alpha-F is characterized by KD : 8.6 X 10(-9)M and N : 1.9 x 10(-13)moles/mg of protein. In conclusion it is felt that 9alpha-F would not be a better "marker" than aldosterone for the renal mineralocorticoid receptors.
D000315:Adrenalectomy; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002855:Chromatography, Thin Layer; D003907:Dexamethasone / Q000378:metabolism; D005438:Fludrocortisone / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011987:Receptors, Steroid / Q000378:metabolism; D014222:Triamcinolone Acetonide / Q000378:metabolism; D014316:Tritium
D011987:Receptors, Steroid; D014316:Tritium; D000450:Aldosterone; D003907:Dexamethasone; D014222:Triamcinolone Acetonide; D005438:Fludrocortisone