2016 Fiscal Year Annual Research Report
Drug discovery platform for improvement of positive inotropic effect in septic myocardium
| Project/Area Number |
15K15661
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| Research Institution | Nagoya University |
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Principal Investigator |
松田 直之 名古屋大学, 医学系研究科, 教授 (50332466)
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| Co-Investigator(Kenkyū-buntansha) |
服部 裕一 富山大学, 大学院医学薬学研究部(医学), 教授 (50156361)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | 敗血症 / 心筋 / 細胞内情報伝達 / ホスホジエステラーゼ / G蛋白 / アデニール酸シクラーゼ |
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| Outline of Annual Research Achievements |
This study evaluated the alteration of cardiac beta-receptor signal using septic mouse model. We weighed the effects of dobutamine and milrinone as inotropes in BALB/c mice with cecal ligation and puncture (CLP)-induced sepsis. Surface expression levels of β1-adrenoceptors and alpha subunits of three main G protein families in myocardium were unaffected by CLP-induced sepsis. Plasma cyclic adenosine monophosphate (cAMP) levels were significantly elevated in both sham-operated and CLP mice in response to milrinone but only in sham-operated controls in response to dobutamine. Of phosphodiesterase (PDE) isoforms, PDE4D, but not PDE3A, both of which are responsible for cardiac cAMP hydrolysis, was significantly upregulated in CLP mouse myocardium.
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