Glucocorticoid action on depolarization-dependent calcium influx in brain synaptosomes.
Synaptic plasma membranes from the brain are known to have specific binding sites for several steroid hormones, but the mechanism of membrane transduction of steroid signals is not understood. In this study, corticosterone was found to stimulate 45Ca2+ uptake in brain synaptosomes upon depolarization of the synaptosomes by high K+ (70 mM). The stimulation of the depolarization-dependent 45Ca2+ uptake by corticosterone is concentration dependent, with the maximal effect occurring at steroid concentration of 5-10 x 10(-7) M (70-80% above control). The EC50 is estimated as 1.3 x 10(-7) M, which is almost identical to the Kd of the specific binding of the steroid to synaptic membranes (1.2 x 10(-7) M) reported previously. The stimulation of 45Ca2+ uptake in brain synaptosomes is specific to corticosterone and other glucocorticoids (cortisol, dexamethasone and triamcinolone); gonadal steroids (17 beta-estradiol, progesterone and testosterone) are ineffective. [3H]Nitrendipine binding was used to examine the effect of corticosterone on voltage-dependent Ca2+ channels. No effect on [3H]nitrendipine binding was found when disrupted synaptic membranes were preincubated with the steroid. However, a significant increase of membrane binding of [3H]nitrendipine was found when intact synaptosomes were first preincubated with the steroid at 37 degrees C and then disrupted. Steroid preincubation of synaptosomes at 0 degrees C was ineffective. Since preincubation at 37 degrees C is required, it appears that metabolic processes modulating Ca2+ channel activity are involved in the steroid action.
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Department of Pharmacology and Molecular Biology, Chicago Medical School, Ill. 60064-3095.
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D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002132:Calcium Radioisotopes; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009568:Nitrendipine / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D015220:Calcium Channels; D002132:Calcium Radioisotopes; D005938:Glucocorticoids; D009568:Nitrendipine; D011188:Potassium; D002118:Calcium; D003345:Corticosterone