TY - JOUR
T1 - Interaction of RU 486, a glucocorticoid and progestin antagonist with human circulating mononuclear leukocytes
AU - Kawai, S.
AU - Brandon, D. D.
AU - Loriaux, D. L.
AU - Chrousos, G. P.
N1 - Funding Information:
From the Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. Supported in part by the Japanese Society of Clinical Pharmacology and Therapeutics, and the Russel-UCLAF Institute. The authors would like to thank Roussel-UCLAF for generously providing RU 486 for this study. Reprint requests: Shinichi Kawai, MD, DEB, NICHD, NIH, Bldg 10, Room 1ON262, Bethesda, MD 20892.
PY - 1989
Y1 - 1989
N2 - 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.
AB - 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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U2 - 10.1097/00000441-198909000-00004
DO - 10.1097/00000441-198909000-00004
M3 - Article
C2 - 2801752
AN - SCOPUS:0024445785
SN - 0002-9629
VL - 298
SP - 167
EP - 171
JO - American Journal of the Medical Sciences
JF - American Journal of the Medical Sciences
IS - 3
ER -