This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Di, S. Articles by Tasker, J. G. Search for Related Content PubMed PubMed Citation Articles by Di, S. Articles by Tasker, J. G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CHOLESTEROL DEXAMETHASONE GLUTAMIC ACID HYDROCHLORIDE

Rapid Glucocorticoid-Mediated Endocannabinoid Release and Opposing Regulation of Glutamate and -Aminobutyric Acid Inputs to Hypothalamic Magnocellular Neurons

Division of Neurobiology (S.D., J.G.T.), Department of Cell and Molecular Biology, and Neuroscience Program (R.M.-L., J.G.T.), Tulane University, New Orleans, Louisiana 70118; and Neuroscience Center of Excellence (V.L.M., N.G.B.), Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112

Address all correspondence and requests for reprints to: Jeffrey G. Tasker, Ph.D., Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana 70118-5698. E-mail: tasker{at}tulane.edu.

Glucocorticoids secreted in response to stress activation of the hypothalamic-pituitary-adrenal axis feed back onto the brain to rapidly suppress neuroendocrine activation, including oxytocin and vasopressin secretion. Here we show using whole-cell patch clamp recordings that glucocorticoids elicit a rapid, opposing action on synaptic glutamate and -aminobutyric acid (GABA) release onto magnocellular neurons of the hypothalamic supraoptic nucleus and paraventricular nucleus, suppressing glutamate release and facilitating GABA release by activating a putative membrane receptor. The glucocorticoid effect on both glutamate and GABA release was blocked by inhibiting postsynaptic G protein activity, suggesting a dependence on postsynaptic G protein signaling and the involvement of a retrograde messenger. Biochemical analysis of hypothalamic slices treated with dexamethasone revealed a glucocorticoid-induced rapid increase in the levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The glucocorticoid suppression of glutamate release was blocked by the type I cannabinoid receptor cannabinoid receptor antagonist, AM251, and was mimicked and occluded by AEA and 2-AG, suggesting it was mediated by retrograde endocannabinoid release. The glucocorticoid facilitation of GABA release was also blocked by AM251 but was not mimicked by AEA, 2-AG, or a synthetic cannabinoid, WIN 55,212–2, nor was it blocked by vanilloid or ionotropic glutamate receptor antagonists, suggesting that it was mediated by a retrograde messenger acting at an AM251-sensitive, noncannabinoid/nonvanilloid receptor at presynaptic GABA terminals. The combined, opposing actions of glucocorticoids mediate a rapid inhibition of the magnocellular neuroendocrine cells, which in turn should mediate rapid feedback inhibition of the secretion of oxytocin and vasopressin by glucocorticoids during stress activation of the hypothalamic-pituitary-adrenal axis.

This article has been cited by other articles:

				M. Kano, T. Ohno-Shosaku, Y. Hashimotodani, M. Uchigashima, and M. Watanabe Endocannabinoid-Mediated Control of Synaptic Transmission Physiol Rev, January 1, 2009; 89(1): 309 - 380. [Abstract] [Full Text] [PDF]

				S. Rossi, V. De Chiara, A. Musella, H. Kusayanagi, G. Mataluni, G. Bernardi, A. Usiello, and D. Centonze Chronic Psychoemotional Stress Impairs Cannabinoid-Receptor-Mediated Control of GABA Transmission in the Striatum J. Neurosci., July 16, 2008; 28(29): 7284 - 7292. [Abstract] [Full Text] [PDF]

				E. R. de Kloet and R. A. Sarabdjitsingh Everything Has Rhythm: Focus on Glucocorticoid Pulsatility Endocrinology, July 1, 2008; 149(7): 3241 - 3243. [Full Text] [PDF]

				M. Christ-Crain, B. Kola, F. Lolli, C. Fekete, D. Seboek, G. Wittmann, D. Feltrin, S. C. Igreja, S. Ajodha, J. Harvey-White, et al. AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushing's syndrome FASEB J, June 1, 2008; 22(6): 1672 - 1683. [Abstract] [Full Text] [PDF]

				J. H. Yang, L. H. Li, S. Y. Shin, S. Lee, S. Y. Lee, S. K. Han, and P. D. Ryu Adrenalectomy Potentiates Noradrenergic Suppression of GABAergic Transmission in Parvocellular Neurosecretory Neurons of Hypothalamic Paraventricular Nucleus J Neurophysiol, February 1, 2008; 99(2): 514 - 523. [Abstract] [Full Text] [PDF]

				G. Rossi, V. Gasperi, R. Paro, D. Barsacchi, S. Cecconi, and M. Maccarrone Follicle-Stimulating Hormone Activates Fatty Acid Amide Hydrolase by Protein Kinase A and Aromatase-Dependent Pathways in Mouse Primary Sertoli Cells Endocrinology, March 1, 2007; 148(3): 1431 - 1439. [Abstract] [Full Text] [PDF]

				R. J. Denver Endocannabinoids Link Rapid, Membrane-Mediated Corticosteroid Actions to Behavior Endocrinology, February 1, 2007; 148(2): 490 - 492. [Full Text] [PDF]

				J. G. Tasker, S. Di, and R. Malcher-Lopes Rapid Glucocorticoid Signaling via Membrane-Associated Receptors Endocrinology, December 1, 2006; 147(12): 5549 - 5556. [Abstract] [Full Text] [PDF]

				A. V. Derbenev, M. J. Monroe, N. R. Glatzer, and B. N. Smith Vanilloid-mediated heterosynaptic facilitation of inhibitory synaptic input to neurons of the rat dorsal motor nucleus of the vagus. J. Neurosci., September 20, 2006; 26(38): 9666 - 9672. [Abstract] [Full Text] [PDF]

				P. Pacher, S. Batkai, and G. Kunos The Endocannabinoid System as an Emerging Target of Pharmacotherapy Pharmacol. Rev., September 1, 2006; 58(3): 389 - 462. [Abstract] [Full Text] [PDF]

				M. G. Kozoriz, J. B. Kuzmiski, M. Hirasawa, and Q. J. Pittman Galanin Modulates Neuronal and Synaptic Properties in the Rat Supraoptic Nucleus in a Use and State Dependent Manner J Neurophysiol, July 1, 2006; 96(1): 154 - 164. [Abstract] [Full Text] [PDF]

				R. Malcher-Lopes, S. Di, V. S. Marcheselli, F.-J. Weng, C. T. Stuart, N. G. Bazan, and J. G. Tasker Opposing crosstalk between leptin and glucocorticoids rapidly modulates synaptic excitation via endocannabinoid release. J. Neurosci., June 14, 2006; 26(24): 6643 - 6650. [Abstract] [Full Text] [PDF]

				S. Di, C. Boudaba, I. R. Popescu, F.-J. Weng, C. Harris, V. L. Marcheselli, N. G. Bazan, and J. G. Tasker Activity-dependent release and actions of endocannabinoids in the rat hypothalamic supraoptic nucleus J. Physiol., December 15, 2005; 569(3): 751 - 760. [Abstract] [Full Text] [PDF]