ZK91587: a novel synthetic antimineralocorticoid displays high affinity for corticosterone (type I) receptors in the rat hippocampus.
In vitro cytosol binding assays have shown the properties of binding of a novel steroid, ZK91587 (15 beta, 16 beta-methylene-mexrenone) in the brain of rats. Scatchard and Woolf analyses of the binding data reveal the binding of [3H] ZK91587 to the total hippocampal corticosteroid receptor sites with high affinity (Kd 1.9 nM), and low capacity (Bmax 17.3 fmol/mg protein). When 100-fold excess RU28362 was included simultaneously with [3H] ZK91587, the labelled steroid binds with the same affinity (Kd 1.8 nM) and capacity (Bmax 15.5 fmol/mg protein). Relative binding affinities (RBA) of various steroids for the Type I or Type II corticosteroid receptor in these animals are: Type I: ZK91587 = corticosterone (B) greater than cortisol (F); Type II: B greater than F much greater than ZK91587. In the binding kinetic study, ZK91587 has a high association rate of binding in the rat (20.0 x 10(7) M-1 min-1). The steroid dissociates following a one slope pattern (t 1/2 30 h), indicating, the present data demonstrate that in the rat hippocampus, ZK91587 binds specifically to the Type I (corticosterone-preferring/mineralocorticoid-like) receptor.
Sutanto
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Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.
de Kloet
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D000818:Animals; D001667:Binding, Competitive; D003345:Corticosterone / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008901:Mineralocorticoids / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011987:Receptors, Steroid; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000378:metabolism
D008901:Mineralocorticoids; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; C024357:corticosterone receptor; D013148:Spironolactone; C054537:ZK 91587; D003345:Corticosterone