| Project/Area Number |
08557136
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
医薬分子機能学
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TAKAISHI Yoshihisa (1997) The University of Tokushima, Fac.Pharmaceut.Sci., Pharmcognosy, Professor, 薬学部, 教授 (60035558)
守時 英喜 (1996) 徳島大学, 薬学部, 教授 (10035545)
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| Co-Investigator(Kenkyū-buntansha) |
ONO Yoshihisa Otsuka Pharmaceut.Co., Institute of Cell Technology, Head researcher, 細胞工学研究所, 研究員
TAKIGUCHI Yoshiharu The University of Tokushima, Fac.Pharmaceut.Sci., Clinical Pharmcology, Associat, 薬学部, 助教授 (40163349)
HISAYAMA Tetsuhiro The University of Tokushima, Fac.Pharmaceut.Sci., Pharmcology, Associate Prof., 薬学部, 助教授 (70130383)
高石 喜久 徳島大学, 薬学部, 教授 (60035558)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 1997: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1996: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | Vascular smooth muscle / Rheumatoid arthritis / Trip toquinone / Nitric oxide / Enzyme induction / Calcium / Endothelium / Tyrosine kinase / メッセンジャーRNA |
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| Research Abstract |
Triptegrium wilfordii var regelli has been used as a traditional Chinese medicine for rheumatoid arthritis. The therapeutic effectiveness of Triptergium wilfordii in a variety of autoimmune diseases including rheumatoid arthritis has been attributed to its immunosuppressive action. Trip toquinone A (TQA) is a principal component of Triptergium wilfordii with a quinoid type diterpene structure. We investigated the effects of TQA on expression of inducible nitric oxide synthase (iNOS) in vascular smooth muscle and on, Ca-mobilization for activation of constitutive type nitric oxide synthase (cNOS) in endothelial cells. TQA inhibited initiation of arginine-induced relaxation, nitrite accumulation, cyclic GMP production and iNOS mRNA transcription primed by LPS- or interleukin-1 in rat aortic muscular strips. These results suggest that TQA prevented expression of the iNOS gene by inflammatory stimuli in vascular smooth muscle cells. On the other hand, TQA inhibited endothelium-dependent cyclopiazonic acid-induced relaxation, but not a relaxation by A23187 or nitroprusside. These pharmacological profiles of TQA were shared by the tyrosine kinase inhibitor herbimycin A with the same structure moiety as TQA.TQA prevented autophosphorylation of tyrosine residues of EGF receptors in A431 cells. Taken together, we propose that TQA is a unique antiinflammatory drug with an inhibitory effect on tyrosine kinase to be involved in induction of iNOS.
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