| Project/Area Number |
62480424
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Kitasato University, School of Pharm.Sci. |
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Principal Investigator |
OH-ISHI Sachiko Kitasato Univ.Sch.Pharm.Sci. Professor, 薬学部, 教授 (70050416)
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| Co-Investigator(Kenkyū-buntansha) |
UTSUNOMIYA Iku Kitasato Univ.Sch.Pharm.Sci. Researcher, 薬学部, 助手 (70168722)
YAMAKI Kohji Kitasato Univ.Sch.Pharm.Sci. Researcher, 薬学部, 助手 (70174597)
HAYASHI Izumi Kitasato Univ.Sch.Pharm.Sci. Lecturer, 薬学部, 講師 (90172999)
HAYASHI Masahiko Kitasato Univ.Sch.Pharm.Sci. Lecturer, 薬学部, 講師 (20164965)
彌益 暁子 北里大学, 薬学部, 助手 (80174697)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | HMW-kininogen / LMW-kininogen / T-kininogen / Inflammation / Rat pleurisy / Kininogen-deficient rat / Eicosanoids / Radioimmunoassay / Tーキニノゲン / 急性相蛋白質 / 性差 / カリクレイン・キニン系 / ブラジキニン / カプトプリル / カラゲニン足浮腫 |
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| Research Abstract |
1. Radioimmunoassays (RIA) of rat high molecular weight (HMW)-, low molecular, weight. (LMW)-kininogen and T-kininogen were developed using specific monoclonal or polyclonal antibodies to these kininogens respectively. By these assays we found that-plasma levels of HMW- and LMW- kininogens of B/N-Katholiek strain rats were 3% of the normal rats (B/N- -Kitasato strain), whereas the levels in the former liver were about 60 % of those of the normal rats. Experiment with hepatocyte primary culture showed that the liver of B/N-Katholiek synthesized the kininogens but could not secrete them into the medium, indicating that the rat has a secretion defect.
2. In the exudate of carrageenin induced pleurisy HMW-kininogen was found to be a form of kinin-free protein by immunoblot analysis. The result suggests that kinin may be released from HMW-kininogen to induce plasma exudation. Furthermore arachidonate metabolites in the exudate was significantly less in the deficient strain in comparison with those in the normal strain, when rats were pretreated with captopril. The result also indicates that there is a pathway of release of eicosanoids through the activation of the kinin system. Thus it proves an important role of the kinin system in inflammation.
3. Rat T-kininogen is a unique kininogen and its level in rat plasma of both strains increased after the inflammation. The plasma level increased 10 - 20 fold at 2-3 days after the carrageenin inflammation. However the rats had increased level of T-kininogen did not show any difference in inflammatory reaction from control rats, indicating that T-kininogen is not pro- or anti-inflammatory -agent. T-kininogen level in female rats was higher than that in male rats and a treatment with estrogen increased T- kininogen level in young rats. The result suggests that there is.a hormonal regulation of biosynthesis of T-kininogen.
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