Regulation of calmodulin content in synaptic plasma membranes by glucocorticoids.
Synaptic plasma membranes (SPM) from the brain are known to have specific binding sites for several steroid hormones, but the mechanisms of membrane transduction of steroid signals is not understood. In this study, corticosterone was found to prevent temperature-dependent dissociation of endogenous calmodulin (CaM) from highly purified SPM from rat cerebral cortex. The steroid stabilizes Ca(2+)-dependent membrane binding of endogenous CaM (78% of total CaM), whereas Ca(2+)-independent binding of CaM (the other 22%) is not affected. The stabilization of membrane binding of endogenous CaM by corticosterone is concentration-dependent, with the maximal effect occurring at steroid concentration of 1 microM. The EC50 is estimated as 130 nM, which is almost identical to the Kd of specific binding of the steroid to SPM (120 nM) reported previously. The effect in stabilizing membrane binding of CaM is specific to corticosterone and other glucocorticoids (cortisol, dexamethasone and triamcinolone); gonadal steroids (17 (17 beta-estradiol, progesterone and testosterone) are ineffective. Furthermore, corticosterone administration in vivo (2 mg/kg, i.p.) produced a rapid increase of CaM content in SPM, occurring within 5 min after steroid injection and persisting for at least 20 min. Since CaM mediates a variety of biochemical processes in synaptic membranes, we hypothesize that the effect of glucocorticoids in promoting membrane binding of CaM may lead to a cascade of consequences in synaptic membrane function.
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Department of Pharmacology and Molecular Biology, Chicago Medical School, Illinois 60064-3095.
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D000818:Animals; D002147:Calmodulin / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D002147:Calmodulin; D005938:Glucocorticoids; D003345:Corticosterone; D006854:Hydrocortisone