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Intracerebroventricular Administration of AT1 Receptor Antisense Oligonucleotides Inhibits the Behavioral Actions of Angiotensin II
Authors:R R Sakai  P F He  X D Yang  L Y Ma  Y F Guo  J J Reilly  C N Moga  S J Fluharty
Institution:Departments of Animal Biology and Pharmacology and Institute of Neurological Sciences, Schools of Medicine and Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.
Abstract:Abstract: Antisense Oligonucleotides were developed to study the expression and function of angiotensin type 1 (AT1) receptors in cultured cells and brain. In both liver epithelial WB and neuro-blastoma N1E-115 cells AT1 antisense oligomers substantially decreased AT1 receptor density, whereas angiotensin type 2 (AT2) receptors remained unchanged. Similarly, repeated intracerebroventricular injections of AT1 antisense oligomers in rats decreased AT1 receptor density in hypothalamic-thalamic-septal tissue, and AT2 receptors were unaffected. Intracerebroventricular antisense oligomers also attenuated drinking elicited by intra-cerebroventricular angiotensin II but not the cholinomimetic carbachol. Collectively, these results demonstrate that antisense Oligonucleotides attenuate angiotensin receptor expression and function in behaving animals.
Keywords:Antisense Oligonucleotides  Angiotensin receptors  Intracerebroventricular administration
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