| Project/Area Number |
17510185
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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 |
Living organism molecular science
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| Research Institution | Mukogawa Women's University |
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Principal Investigator |
ISHIGURO Kyoko Mukogawa Women's University, School of pharmacy and Pharmaceutical Sciences, Professor, 薬学部, 教授 (70151363)
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| Co-Investigator(Kenkyū-buntansha) |
OKU Hisae Mukogawa Women's University, School of pharmacy and Pharmaceutical Sciences, Assistant, 薬学部, 助手 (90281518)
ISHIGURO Masaji SUNTRY, Institute for Boiorganic Research, Chief Scientist, 部長研究員 (10280687)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | Blood flow monitoring / Hen-egg white lysozyme / iNOS KO mouse / inducible NO synthase (iNOS) / e NOS (6) COX-1 and 2 / Allergy preventive medicines / in vivo assay system / in vivoアッセイ法 / NO / COX-1、2 / PGI_2 |
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| Research Abstract |
Our in vivo assay system developed to search for allergy-preventive substances, assesses the blood flow decrease in tail vein microcirculation of mice subjected to sensitization with hen-egg white lysozyme (HEL). The blood flow decrease appears to be regulated by various factors such as nitric oxide (NO), thromboxane (TX) A2, prostacyclin (PGI2) and endothelin (ET)-1 together with cyclooxygenase (COX)-1, 2, and inducible nitric oxide synthase (iNOS).
In this study, we examined in detail the roles of iNOS in this assay system using an iNOS knockout (KO) mouse. We found that the blood flow decrease in the HEL-sensitized iNOS KO mice was slightly weaker than that in their wild type (WT) mice. This blood flow decrease was not affected by a selective COX-1 inhibitor, a COX-2 inhibitor and a PGI2 agonist unlike the case of the WT mice. However, it was inhibited by a nonselective NOS inhibitor, a specific TXA2 synthase inhibitor and a specific ET-1 receptor blocker as in the case of the WT mice. The present results indicate that the blood flow decrease occurs via two pathways; one is an iNOS-independent response involving TXA2 and ET-1, and the other is an iNOS-dependent response involving COX-1, COX-2 and PGI2. Constitutive nitric oxide synthase (cNOS) appears to play some roles in the blood flow decrease and iNOS acts as an exacerbation factor. Our method using HEL-sensitized should be useful for searching for agents that can prevent allergy via new mechanisms.
The other hand we also demonstrated allergy-preventive activity of extract of Populus sieboldii, Xanthorrhoea hastilis and Lonicera japonica using this in vivo assay system. By bioassay-directed fractionation of these plans, new allergy-preventive compounds were isolated.
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