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Research Summary: Our research focuses on the cellular and molecular mechanisms of angiotensis II (Ang II) action in the brain. In particular, radio ligand binding techniques, quantitative autoradiography, and immunocytochemistry are used to determine the localization of AngII receptors in the central nervous system, and biochemical techniques are then used to determine receptor coupling to ion phosphatidylinositol hydrolysis, in cultured neurons. Recent efforts include purification of neuronal AngII receptors, the development of receptor-directed polyclonal and monoclonal antibodies, as well as the cloning of the gene(s) which encode for these receptors. These molecular tools are then used to study the transcriptional and port-translational control of AngII receptor expression as it relates to the behavioral actions of this neuropeptide. Key References: Sakai, R.R., Ma, L.Y., Zhang, D.M., McEwen, B.S. and Fluharty, S.J.: Antisense oligonucleotides inhibit mineralocorticoid receptor expression and function in the brain. Neuroendocrinology, 4:425-429, 1996. Yee, D.K., He, P., Yang, X., Reagen, L.P., Hines, J., Siemens, I.R., Fluharty, S.J.: Cloning and expression of angiotensis II type 2 (AT2) receptors from murine neuroblastoma N1E-115 cells: evidence for AT2 receptor heterogeneity. Molec. Brain Res. 45:108-116, 1997. Heerding, J.N., Yee, D.K., Jacobs, S.L., Fluharty, S.J.: Mutational analysis of the angiotensis II type 2 receptor: contribution of conserved extracellular amino acids. Regul. Peptides 72:97-103, 1997. Flanagan-Cato, L.M., Fluharty, S.J.: Emerging mechanisms of the behavioral effects of steroids. Current Opinion in Neurobiology 7:765-916, 1997.
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