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.
Wright
M C
MC
DH Dept Toxicology, St Bartholomew's Hospital Medical School, London, UK.
Paine
A J
AJ
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