Characteristics of a membrane-associated steroid binding site in rat liver.
The glucocorticoid dexamethasone binds a site in microsomes in a saturable manner which by competition studies also binds other classes of steroids. The characteristics of dexamethasone binding to microsomes is distinct from the cytosolic glucocorticoid receptor by virtue of a slower rate of association; a differential competition by the glucocorticoid receptor agonist triamcinolone acetonide and antagonist RU38486; and a lack of sensitivity to the reversible thiol reactive agent arsenite. However, both binding sites have a similar rate constant for complex dissociation; are sensitive to covalent thiol modification by N ethylmaleimide and iodoacetamide; and have a similar concentration-dependent sensitivity to the reversible thiol reactive agent methyl methanethiosulfonate. The binding of dexamethasone by microsomes therefore exhibits distinct properties from the soluble glucocorticoid receptor.
DH Dept Toxicology, St Bartholomew's Hospital Medical School, London, UK.
M C
MC
Wright
A J
AJ
Paine
D000818:Animals; D001665:Binding Sites; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013256:Steroids / Q000378:metabolism; D014222:Triamcinolone Acetonide / Q000494:pharmacology
D011965:Receptors, Glucocorticoid; D013256:Steroids; D015735:Mifepristone; D003907:Dexamethasone; D014222:Triamcinolone Acetonide