Glucocorticoid actions on synaptic plasma membranes: modulation of [125I]calmodulin binding.
The effects of corticosterone on Ca(2+)-dependent binding of [125I]calmodulin to purified synaptic plasma membranes (SPM) from rats brain were characterized. The enhancement of [125I]calmodulin binding was a sigmoidal function of steroid concentration, with the maximal increase (> 55% above control) occurring at a steroid concentration of 1 x 10(-6) M and EC50 estimated at 1-2 x 10(-7) M. Other glucocorticoids including hydrocortisone, dexamethasone and triamcinolone produced similar effects, whereas steroids without glucocorticoid activity such as 11-deoxycortisol, 11-deoxycorticosterone and cholesterol were ineffective. The steroid-induced increase of binding was correlated with an increase of membrane affinity for [125I]calmodulin as shown by Scatchard analysis, and a decrease of the rate of dissociation of [125I]calmodulin from the membranes as shown by kinetic analysis. Arrhenius analysis indicates that [125I]calmodulin binding was influenced by lipid transition of the membranes and that corticosterone resulted in a shift of membrane transition toward a higher temperature. Since a variety of biochemical processes associated with synaptic membranes are dependent upon calmodulin for their regulation, we hypothesize that the effects of glucocorticoids in promoting membrane binding of calmodulin may lead to a cascade of alterations in synaptic function.
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Department of Pharmacology and Molecular Biology, Chicago Medical School, IL 60064.
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D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013570:Synaptic Membranes / Q000187:drug effects* / Q000378:metabolism*; D013816:Thermodynamics; D014221:Triamcinolone / Q000494:pharmacology
D002147:Calmodulin; D005938:Glucocorticoids; D007457:Iodine Radioisotopes; D014221:Triamcinolone; D003907:Dexamethasone; D002118:Calcium; D003345:Corticosterone; D006854:Hydrocortisone