The glucocorticoid and progestin antagonist, RU 486 (17 β-hydroxy-11β-[4-dimethylaminophenyl]-17α-[1-propynyl]-estra-4, 9-dien-3-one), antagonizes the suppressive effect of dexamethasone on [14C]2-deoxyglucose uptake by intact human mononuclear leukocytes in a concentration-dependent fashion. The authors found at least two types of specific-binding sites for this compound in the mononuclear leukocytes. The first type of sites (receptor content [Ro], 10.8 ± 1.6 fmoles/106 cells [mean ± SD of 4 experiments]; equilibrium dissociation constant (Kd), 0.3 ± 0.1 nM) have a capacity similar to that of the dexamethasone binding site (Ro, 11.2 fmoles/106 cells; Kd, 1.2 nM). The second type of sites (Ro, 56 ± 27 fmoles/106 cells: Kd, 19 ± 5 nM) have a higher capacity and lower affinity for RU 486 than the first type of sites and do not interact with dexamethasone. The authors were unable to demonstrate the presence of the second type of binding sites in subcellular fractions. This finding suggests that site is unstable and lost in the fractionation process. The role of the second type of low-affinity, high-capacity RU 486 specific-binding site in intact human mononuclear leukocytes, as well as its possible occurrence in other tissue, requires further investigation.
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