| Project/Area Number |
25461201
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Kinki University |
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Principal Investigator |
KUME Hiroaki 近畿大学, 医学部, 准教授 (50303631)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | 喘息 / phenotype change / 気道平滑筋 / G protein / Ca2+ signaling / KCa channel / Rho-kinase / allosteric effect / beta2 アドレナリン受容体 / ムスカリン受容体 / イオンチャネル / Ｇ蛋白 / Ca2+ 動態 / COPD / 気管支喘息 / β2アドレナリン受容体耐性化 / 気道過敏性亢進 / Ca2+チャネル / 細胞内Ca2+ 動態 / 細胞内Ca2+ 感受性 / β2アドレナリン受容体 / 気道過敏性 / 気道リモデリング |
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| Outline of Final Research Achievements |
Alteration of contractility in airway smooth muscle (ASM) contributes to airflow limitation, airway hyperresponsiveness (AHR), and beta2-adrenergic desensitization. Alteration of synthesis contributes to airway remodeling via facilitation of the proliferation and migration in ASM. In our observation, Ca2+ dynamics through the large-conductance Ca2+-activated K+ channel/L-type voltage-dependent Ca2+ channel linkage, and Ca2+ sensitization through the RhoA/Rho-kinase pathway contribute not only to alterations in the contractile phenotype involved in airflow limitation, AHR and tolerance to beta2-adrenergic receptors, but also to alteration of the synthetic phenotype involved in airway remodeling. The Ca2+ signaling also contribute to the synergism (cross talk) in combination of beta2-adrenergic receptor agonists with muscarinic receptor antagonists. Therefore, the phenotype change in ASM via the Ca2+ signaling may be a novel target for development of asthmatic agents.
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