Abstract
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 calmodlin (CaM) from highly purified SPM from rat cerebral cortex. The steroid stabilizes Ca2+-dependent membrane binding of endogenous CaM (78% of total CaM), whereas Ca2+-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 μM. 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 (17β-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.
Similar content being viewed by others
References
Baulieu, E.-E., and Robel, P. 1990. Neurosteroids: A new brain function? J. Steroid Biochem. Molec. Biol. 37:395–403.
Paul, S. M., and Purdy, R. H. 1992. Neuroactive Steroids. FASEB J. 6:2311–2322.
Carson-Jurica, M. A., Schrader, W. T., and O'Malley, W. 1990. Steroid receptor family: Structure and functions. Endocrine Rev. 11:201–220.
Reichel, R. R., and Jacob, S. T. 1993. Control of gene expression by lipophilic hormones. FASEB J. 7:427–436.
Duval, D., Durant, S., and Homo-Delarche, F. 1983. Non-genomic effects of steroids: Interactions of steroid hormone molecules with membrane structrues and functions. Biochim. Biophys. Acta. 737: 409–442.
Szego, C. M. 1984. Mechanisms of hormone action: Parallels in receptor-mediated signal propagation for steroids and peptide effectors. Life Sci. 35:2383–2396.
Szego, C. M., and Pietras, R. J. 1984 Lysosomal functions in cellular activation: Propagation of the actions of hormones and other effectors. Internat. Rev. Cytol. 84:1–302.
Sze, P. Y., and Iqbal, Z. 1994. Glucocorticoid actions on synaptic plasma membranes: Modulation of [125I]calmodulin binding. J. Steroid Biochem. Molec. Biol. 48:179–186.
Majewska, M. D., Harrison, N. L., Schwartz, R. D., Barker, J. L., and Paul S. M. 1984. Steroid horome metabolites are barbiturate-like modulators of the GABA receptor. Science (N.Y.) 231:1004–1007.
Majewska, M. D., and Schwartz, R. D. 1987. Pregnenolone-sulfate: an endogenous antagonist of the γ-aminobutyric acid receptor complex in brain? Brain Res. 404:355–360.
Majewska, M. D. 1987. Antagonist-type interaction of glucocorticoids with the GABA receptor-coupled chloride channel. Brain Res. 418:377–382.
Gee, K. W., Bolger, M. B., Brinton, R. A., Coirini, H., and McEwen, B. S. 1988. Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action. J. Pharmacol. Exp. Ther. 248: 803–812.
Lopez-Colome, A. M., McCarthy, M., and Beyer, C. 1990. Enhancement of [3H]muscimol binding to brain synaptic membrane by progesterone and related pregnanes. Eur. J. Pharmacol. 176: 297–303.
Lan, N. C., Chen, J.-S., Belelli, D., Pritchett, D. B., Seeburg, P. H., and Gee, K. W. 1990. A steroid recognition site is functionally coupled to an expressed GABAA-benzodiazepine receptor. Eur. J. Pharmacol. 188:403–406.
Morrow, A. L., Pace, J. R., Purdy, R.H., and Paul, S. M. 1990. Characterization of steroid interactions with γ-aminobutyric acid receptor-gated chloride ion channels: Evidence for multiple steroid recognition sites. J. Pharmacol. Exp. Ther. 37:263–270.
Valera, S., Ballivet, M., and Bertrand, D. 1992. Progesterone modulates a neuronal nicotinic acetylcholine receptor. Proc. Natl. Acad. Sci. (U.S.A.) 89:9949–53.
Petitti, N., and Etgen, A. M. 1992. Progesterone promotes rapid desensitization of α1-adrenergic receptor augmentation of cAMP formation in rat hypothalamic slices. Neuroendocrinology 55:1–8.
Su, T.-P., London, E. D., and Jaffe, J. H. 1988. Steroid binding at σ receptors suggests a link between endocrine, nervous, and immune systems. Science (N.Y.) 240:219–221.
Schwarz, S., Pohl, P., and Zhou, G.-Z. 1989. Steroid binding at σ-“opioid” receptors. Science (N.Y.) 246:1635–1636.
Hua, S.-Y., and Chen, Y.-Z. 1989. Membrane receptor-mediated electrophysiological effects of glucocorticoid on mammalian neurons. Endocrinology 124:687–691.
Nabekura, J., Oomura, Y., Minami, T., Mizuno, Y., and Fukuda, A. 1986. Mechanism of the rapid effects of 17β-estradiol on medial amygdala neurons. Science (N.Y.) 233:226–228.
Schumacher, M., Coirini, H., Pfaff, D. W., and McEwen, B. S. 1990. Behavioral effects of progesterone associated with rapid modulation of oxytocin receptors. science (N.Y.) 250:691–694.
Towle, A. C., and Sze, P. Y. 1983. Steroid binding to synaptic plasma membrane: Differential binding of glucocorticoid and gonadal steroids. J. Steroid Biochem. 18:135–143.
Sze, P. Y., and Towle, A. C. 1993. Developmental profile of glucocorticoid binding to synaptic plasma membrane from rat brain. Int. J. Dev. Neurosci. 11:339–346.
Orchinik, M., Murray, T. F., and Moore, F. L. 1991. A corticosteroid receptor in neuronal membranes. Science (N.Y.) 252: 1848–1851.
Orchinik, M., Murray, T. F., Franklin, P. H., and Moore, F. L., 1992. Guanyl nucleotides modulate binding to steroid receptors in neuronal membranes. Proc. Natl. Acad. Sci. (U.S.A.) 89:3830–3934.
Ke, F.C., and Ramirez, V. D. 1990. Binding of progesterone to nerve cell membrane of rat brain using progesterone conjugated to125I-bovine serum albumin as a ligand J. Neurochem. 54:467–472.
Tischkau, S. A., and Ramirez, V. D. 1993. A specific membrane binding protein for progesterone in rat brain: Sex differences and induction by estrogen. Proc. Natl. Acad. Sci. (U.S.A.) 90:1285–1289.
Iqbal, Z., and Sze, P. Y. 1993. [125I]Calmodulin binding to synaptic plasma membranes from rat brain: Kinetic and Arrhenius analysis. Neurochem. Res. 18:897–905.
Chafouleas, J. G., Dedman, J. R., Munjaal, R. P., and Means, A. R. 1979. Calmodulin: Development and application of a sensitive radioimmunoassay. J. Biol. Chem. 254:10262–10267.
Wallace, R. W., and Cheung, W. Y. 1979. Calmodulin: Production of an antibody in rabbit and development of a radioimmunoassay. J. Biol. Chem. 254:6564–6571.
Teshima, Y., and Kakiuchi, S. 1978. Membrane-bound forms of Ca2+-dependent protein modulator: Ca2+-dependent and-independent bindings of modulator protein to the particulate fraction from brain. J. Cyclic Nucleotide Res. 4:219–231.
Lau, Y. S. and Gnegy, M. E. 1980. Effects of lanthanum and trifluoperazine on [125I]calmodulin binding to rat striatal particulates. J. Pharmacol Exp. Therap. 215:28–34.
Minocherhomjee, A. M., Shattuck, R. L., and Storm, D. R. 1988. Calmodulin-stimulated adenylate cyclases, in Calmodulin, Molecular Aspects of Cellular Regulations, Vol. 5 (Cohen, P., and Klee, C. B. eds.) pp. 249–263, Elsevier, New York.
Klee, C. B., and Vanaman, T. C. 1982. Calmodulin. Adv. Protein Chem. 35:213–322.
Kakiuchi, S. 1983. Calmodulin-binding proteins in brain. Neurochem. Internat. 5:159–169.
Cimler, B. M., Andreasen, T. J., Andreasen, K. I. and Storm D. R. 1985. P-57 is a neural specific, calmodulin-binding protein. J. Biol. Chem. 260:10784–10788.
Cohen, P., and Klee, C. B. 1988. Calmodulin, Molecular Aspects of Cellular Regulation, Vol. 5, Elsevier, New York.
Means, A. R., VanBerkum, M. F., Bagchi, I., Lu, K. P., and Rasmussen, C. D. 1991. Regulatory functions of calmodulin. Pharmacology & Therapeutics. 50:255–270.
Sze, P. Y., and Iqbal, Z. 1994. Glucocorticoid action, on depolarization-dependent calcium influx in brain synaptosomes. Neuroendocrinology 59:457–465.
Chang, C. F., Gutierrez, L. M., Mundina-Weilenmann, C., and Hosey, M. M. 1991. Dihydropyridine-sensitive calcium channels from skeletal muscle. II. Functional effects of differential phosphorylation of channel subunits. J. Biol. Chem. 266:16395–16400.
Author information
Authors and Affiliations
Additional information
Special issue dedicated to Dr. Sidney Ochs.
Rights and permissions
About this article
Cite this article
Sze, P.Y., Iqbal, Z. Regulation of calmodulin content in synaptic plasma membranes by glucocorticoids. Neurochem Res 19, 1455–1461 (1994). https://doi.org/10.1007/BF00972475
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00972475