Interaction of RU 486, a glucocorticoid and progestin antagonist with human circulating mononuclear leukocytes

The glucocorticoid and progestin antagonist, RU 486 (17 beta-hydroxy-11 beta-[4-dimethylaminophenyl]-17 alpha-[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/10(6) 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/10(6) cells; Kd, 1.2 nM). The second type of sites (Ro, 56 +/- 27 fmoles/10(6) 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 this 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.