| Project/Area Number |
13670101
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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 |
General pharmacology
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| Research Institution | Hoshi University |
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Principal Investigator |
MISAWA Miwa Hoshi University, School of Pharmacy, Professor, 薬学部, 教授 (20061294)
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| Co-Investigator(Kenkyū-buntansha) |
CHIBA Yoshihiko Hoshi University, School of Pharmacy, Research Assistant, 薬学部, 助手 (00287848)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | bronchial asthma / airway hvperesponsiveness / RhoA / Ca^<2+> sensitization / Rho kinase / Rho A / CPI-17 / 三量体Gタンパク質 |
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| Research Abstract |
1. When bronchial smooth muscle contracted by ACh in normal rats, a monomeric GTP binding protein, RhoA, translocated to plasma membrane (RhoA activation). The bronchial muscle from repeatedly antigen-challenged rats more markedly contracted by ACh, and the RhoA activation was also more markedly augmented in the muscle. These suggest that augmentation of RhoA activation may be a crucial factor in airway hyperresponsiveness at allergic bronchial asthma.
2. In β-escin-penneabilized intrapulmonary bronchial smooth muscle, ACh induced a further contraction under the same [Ca^<2+>]_i, i.e. Ca^<2+> sensitization. Rho kinase (ROCK) inhibitor, Y-27632, completely blocked the Ca^<2+> sensitization, suggesting that RhoA/ROCK-mediated Ca^<2+> sensitization may be involved in the airway hyperesponsiveness.
3. An augmentation of ACh-induced contraction of antigen-challenged bronchial smooth muscle was obviously observed, but that of tracheal smooth muscle was not. This correlated the fact that RhoA expression in bronchial, but not tracheal, smooth muscle was significantly increased in the antigen-treated rats. This suggests that the increased expression of RhoA has an important role in developing hyperesponsiveness of bronchial smooth muscle.
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