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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.