1999 Fiscal Year Final Research Report Summary
Regulation of endothelin and NO on airway wall remodelling
| Project/Area Number |
10672063
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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 | Nihon University |
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Principal Investigator |
KIZAWA Yasuo College of Pharmacy, Nihon University, Lecturer, 薬学部, 講師 (80211192)
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| Project Period (FY) |
1998 – 1999
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| Keywords | remodelling / endothelin / NO / bronchus / smooth muscle / cultured cells |
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| Research Abstract |
1. Effects of endothelin-1 (ET-1) and nitric oxide (NO) on the proliferation of cultured guinea pig bronchial smooth muscle were performed by using MTT assay and cell count. ET-1 alone augmented cell proliferation, and also potentiated the effect of epidermal growth factor (EGF) in a concentration-dependent manner. An ETィイD2AィエD2 antagonist, BQ-123, reduced the cell-proliferative effect of ET-1. Furthermore, the cell-proliferative action of ET-1 was partly reduced by a nitric oxide (NO) donor, SIN-1. These results suggest that ET-1 acts not only as a co-mitogen with EGF but also as a mitogen alone, and that its action is mediated through activation of ETィイD2AィエD2 receptors. In addition, the activity may be partly reduced by NO. Therefore, ET-1 may contribute to airway remodelling, a pathophysiological hallmark of asthma.
2. Whether ET-1 regulated NO synthesis by the inducible isoform of NO synthase (iNOS) in cultured bronchial smooth muscle cells of guinea pig, using an immunocytochemical technique was in vestigated. In the cultured bronchial cells, constitutive NOS (eNOS) was detected, but iNOS was not found. Exposure to ET-1 for 72 h induced iNOS, and the induction was inhibited by BQ-123. These results suggest that ET-1 induces iNOS via ETィイD2AィエD2 receptor activation in guinea pig bronchial smooth muscle cells. Thus ET-1 may stimulate NO formation not only in epithelial but also smooth muscle cells.
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