2006 Fiscal Year Final Research Report Summary
The new pathophysiological role and its mechanism of angiotensin receptor
| Project/Area Number |
17590052
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Takasaki University of Health and Welfare (2006)
Tohoku University (2005) |
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Principal Investigator |
YOSHIDA Makoto Takasaki University of Health and Welfare, Faculty of Pharmacy, Professor, 薬学部, 教授 (90201011)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAHATA Norimichi Tohoku University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (60045804)
HONMA Shigeyoshi Takasaki University of Health and Welfare, Faculty of Pharmacy, Research instructor, 薬学部, 助手 (20344682)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Angiotensin / Pharmacology / Physiology |
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| Research Abstract |
To investigate the new pathophysiological role and its mechanisms of angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R), we used MDCKII cell, a renal epithelial cell line, and PC-12 cell, a pheochromocytoma cell. In MDCKII cell stably transfected with rat AT2R, the stimulation with angiotensin II (Ang II) inhibited forskolin-induced cyclic AMP accumulation with dose-dependent manner. This inhibition was abolished by co-treatment with PD123319, a AT2R antagonist, or pre-treatment of pertussis toxin, suggesting the perticipation of the Gi protein-coupled mechanism of AT2R stimulation. The stimulation of this cell with Ang II under treatment AT1R antagonist activated the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Ang II reduced mRNA and protein level of AT2R in PC-12 cells transiently expressed rat AT1R. Double transfection of AT1AR and AT2R on PC-12 cells induced the Ang II-induced internalization of AT2R. These results suggest that 1) AT2R affect cell growth through activation of ERK 1/2 with Gi protein-coupled mechanism, 2) AT1R affect the AT2R expression with some unknown mechanism. Based on these results, further investigations using whole animal should be needed for clarify the pathophysiological role of AT2R.
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Research Products
(1 results)
