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Department of Physiology and Functional Genomics, College of Medicine, and McKnight Brain Institute, University of Florida, Gainesville, Florida 32610
Address all correspondence and requests for reprints to: Colin Sumners, Ph.D., Department of Physiology, University of Florida, 1600 SW Archer Road, P.O. Box 100274, Gainesville, Florida 32610. E-mail: csumners{at}phys.med.ufl.edu
Previously we determined that angiotensin II (Ang II) activates neuronal AT1 receptors, located in the hypothalamus and the brainstem, to stimulate noradrenergic pathways. To link Ang II to the regulation of norepinephrine metabolism in neurons cultured from newborn rat hypothalamus and brainstem we have used cDNA arrays for high throughput gene expression profiling. Of several genes that were regulated, we focused on macrophage migration inhibitory factor (MIF), which has been associated with the modulation of norepinephrine metabolism. In the presence of the selective AT2 receptor antagonist PD123,319 (10 µM), incubation of cultures with Ang II (100 nM; 124 h) elicited an increase in MIF gene expression. Western immunoblots further revealed that Ang II (100 nM; 124 h) increased neuronal MIF protein expression. This effect was inhibited by the AT1 receptor antagonist losartan (10 µM), the PLC inhibitor U-73122 (10 or 25 µM), the PKC inhibitor chelerythrine (10 µM), and the Ca2+ chelator 1,2-bis-[2-aminophenoxy]-ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester (10 µM). Taken together with our observation that MIF is expressed in the terminal fields of noradrenergic neurons (hypothalamus) and that Ang II increases the expression of MIF in this region in vivo, our data may suggest a novel role of Ang II in norepinephrine metabolism.
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T. Matsuura, R. A. Harrison, A. D. Westwell, H. Nakamura, A. E. Martynyuk, and C. Sumners Basal and angiotensin II-inhibited neuronal delayed-rectifier K+ current are regulated by thioredoxin Am J Physiol Cell Physiol, July 1, 2007; 293(1): C211 - C217. [Abstract] [Full Text] [PDF] |
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H. Li, Y. Gao, C. D. Freire, M. K. Raizada, G. M. Toney, and C. Sumners Macrophage migration inhibitory factor in the PVN attenuates the central pressor and dipsogenic actions of angiotensin II FASEB J, August 1, 2006; 20(10): 1748 - 1750. [Abstract] [Full Text] [PDF] |
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C. Sun, H. Li, L. Leng, M. K. Raizada, R. Bucala, and C. Sumners Macrophage Migration Inhibitory Factor: An Intracellular Inhibitor of Angiotensin II-Induced Increases in Neuronal Activity J. Neurosci., November 3, 2004; 24(44): 9944 - 9952. [Abstract] [Full Text] [PDF] |
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M. Ogier, L. Bezin, J.-M. Cottet-Emard, M. Bader, M. Vincent, J.-M. Pequignot, J. McGregor, and G. Bricca Delayed Maturation of Catecholamine Phenotype in Nucleus Tractus Solitarius of Rats With Glial Angiotensinogen Depletion Hypertension, November 1, 2003; 42(5): 978 - 984. [Abstract] [Full Text] [PDF] |
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M. A. Fleegal and C. Sumners Drinking behavior elicited by central injection of angiotensin II: roles for protein kinase C and Ca2+/calmodulin-dependent protein kinase II Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2003; 285(3): R632 - R640. [Abstract] [Full Text] [PDF] |
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H. Liao, R. Bucala, and R. A. Mitchell Adhesion-dependent Signaling by Macrophage Migration Inhibitory Factor (MIF) J. Biol. Chem., January 3, 2003; 278(1): 76 - 81. [Abstract] [Full Text] [PDF] |
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