1998 Fiscal Year Final Research Report Summary
Gene regulation and biophysiological significance of angiotensin type 2 receptor
| Project/Area Number |
09470175
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kansai Medical University |
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Principal Investigator |
MATSUBARA Hiroaki Kansai Medical University, Associate Professor, 医学部, 講師 (10239072)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Yasukiyo Kansai Medical University, Assistant Professor, 医学部, 助手 (40268371)
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| Project Period (FY) |
1997 – 1998
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| Keywords | angiotensin II / angiotensin II receptor / angiotensin AT2 receptor / angiotensin AT1 receptor |
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| Research Abstract |
The receptors for angiotensin (Ang) II are classified into Iwo subtypes (AT1-R and AT2-R) by the discovery of non-peptidic ligands and AT1-R mediates most of the cardiovascular actions of Ang II.AT2-R is expressed at very high levels in the developing fetus, whereas in the adult its expression in the cardiovascular system is very low. The expression of AP2-R can be modulated by pathological states associated with tissue remodeling or inflammation. In failing hearts or neointima formation after vascular injury, AT2-R is re-expressed in cells proliferating in interstitial regions or neointima and exerts an inhibitory effect on Ang II-induced mitogen signals or synthesis of extracellular matrix proteins, resulting in attenuation of the tissue remodeling. An extreme way of cell growth inhibition directs cells into programmed cell death, and its process initiated by withdrawal of growth factors is also enhanced by AT2-R.Cardiac myocyte- or vascular smooth muscle-specific overexpression mice of AT2-R display an inhibitory effect on Ang II-induced chronotropic or pressor actions, suggesting the role of AT2-R on the activity of cardiac pacemaker cells or maintenance of vascular resistance. AT2-R also activates the kinin/nitric oxide/cGMP system in the cardiovascular and renal system, resulting in the AT2-R-mediated cardioprotection, vasodilation and pressure nairiuresis. These effects transmitted by AT2-R are mainly exerted by stimulation of protein tyrosine or serine/threonine phosphatases in Gi-protein dependent manner. The expression level of AT2-R is much higher in human hearts than in those of rodents, and the AT2-R-mediated actions are likely enhanced, especially by clinical application of AT1-R antagonists.
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[Publications] Murasawa S,Matsubara H,Mori Y,Nozawa Y,Gotoh N,Shibuya M,Masaki H,Maruyama K,Tsutsumi Y,Moriguchi Y,Shibazaki Y,Tanaka Y,Iwasaka T,Inada M: "Angiotensin II type 1 receptor-induced extracellular signal-regulated protein kinase activation is mediated by Ca2+/calmodulin-dependent transactivation of epidermal growth factor receptor." Circ Res. 29 ; 82. 1338-48 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Masaki H,Kurihara T,Yamaki A,Inomata N,Nozawa Y,Mori Y,Murasawa S,Kizima K,Maruyama K,Horiuchi M,Dzau VJ,Takahashi H,Iwasaka T,Inada M,Matsubara H: "Cardiac-Specific Overxpression of Angiotensin AT2 receptor Causes Attenuated Response to AT1 receptor-Mediated Pressor and Chronotropic Effects" J Clin Invest. 101. 527-535 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Ohkubo N,Matsubara H,Nozawa Y,Mori Y,Murasawa S,Kijima K,Maruyama K,Masaki H,Tsutumi Y,Shibazaki Y,Iwasaka T,Inada M: "Angiotensin Type 2 Receptors Are Re-expressed by Cardiac Fibroblasts from Failing Myopathic Hearts and Inhibit Cell Growth and Fibrillar Collagen Metabolism" Circulation. 96. 3954-3962 (1997)
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[Publications] Mori Y,Matsubara H,Murasawa S,Kijima K,Maruyama K,Tsukaguchi H,Okubo N,Hamakubo T,Inagami T,Iwasaka T,Inada M: "Translational regulation of angiotensin II type 1A receptor : Role of upstream AUG triplets" Hypertension. 28. 810-817 (1996)
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