Intracerebroventricular Administration of AT1 Receptor Antisense Oligonucleotides Inhibits the Behavioral Actions of Angiotensin II |
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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 |
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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. |
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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. |
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Keywords: | Antisense Oligonucleotides Angiotensin receptors Intracerebroventricular administration |
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