タモキシフェンはMAPKの抑制を介してラット大動脈平滑筋を弛緩させる(薬理学)

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概要

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• 非ステロイド性・合成抗エストロジェン薬であるタモキシフェンによって引き起こされるラット大動脈平滑筋の弛緩反応おけるmitogen-activated protein kinase(MAPK)経路の関与を調べた.タモキシフェン(0.1-300μM)はエンドセリン-1(ET-1,3nM)によって引き起こされた大動脈平滑筋の収縮を濃度依存性に抑制した.タモキシフェンの抑制作用は10μMICI182,780,選択的エストロジェン受容体アゴニスト,によって減弱されなかった.Ca^<2+>チャネル遮断薬であるベラパミル(1μM)前処置標本においても,タモキシフェンはET-1による収縮を抑制した.PDO98059とSB203580,それぞれMAPK/extracellular signal-regulated kinase(ERK)kinaseとp38 MAPK阻害薬,は共にET-1による大動脈平滑筋の収縮を抑制した.抗燐酸化MAPK抗体を用いたウェスタンブロット解析において,ET-1(3nM)は大動脈筋条片におけるERK1/2とp38 MAPK活性をともに増強し,この反応は4mM EGTA処置によっては減弱されなかった.タモキシフェン(100μM)はET-1(3nM)によるERK1/2とp38 MAPK活性増加を抑制したが,これらキナーゼの発現量を大きく変化させなかった.これらの結果より,タモキシフェンはラット血管平滑筋を弛緩させ,この作用の一部はca^<2+>非依存性MAPK経路の抑制に起因することが示唆される.

• 社団法人日本獣医学会の論文
• 2003-11-25

著者

• LEE Sang-rae

  Hallym大学医学部動物実験センター

• Lee So

  韓国

• Won Kyung-jong

  Department Of Physiology & Immunology School Of Medicine Konkuk University

• Kim Bokyung

  Department Of Physiology & Immunology School Of Medicine Konkuk University

• Kim B.

  韓国

• Kim Bokyung

  College Of Medicine Konkuk University

• KWON Seongchun

  Department of Physiology, College of Medicine, Kwandong University

• Kwon Seongchun

  Department Of Physiology College Of Medicine Yonsei University

• Kwon Seongchun

  Department Of Physiology Kwandong University College Of Medicine

• Kim Jin-hyun

  Department Of Veterinary Pathology College Of Veterinary Medicine And Agricultural Biotechnology Seo

• KIM Junghwan

  Department of Physical Therapy, College of Natural Science, Yongin University

• CHO SungIl

  Department of Physiology and Anesthesiology, College of Medicine, Institute of Biomedical Science an

• PARK Sohyun

  Department of Veterinary Physiology, College of Veterinary Medicine, Konkuk University

• LEE Sangmo

  Department of Veterinary Physiology, College of Veterinary Medicine, Konkuk University

• Lee Sangmo

  Department Of Life Science College Of Biomedical & Health Science Konkuk University

• Cho Sungil

  Department Of Physiology And Anesthesiology College Of Medicine Institute Of Biomedical Science And

• Park Sohyun

  Department Of Veterinary Physiology College Of Veterinary Medicine Konkuk University

• Kim Bokyung

  韓国

• Kim Junghwan

  Department Of Physiology & Immunology School Of Medicine Konkuk University

• Kim Junghwan

  Department Of Physical Therapy College Of Natural Science Yongin University

• Kim Bongtae

  Department Of Veterinary Pathology College Of Veterinary Medicine And School Of Agicultural Biotechn

• Kim J.

  Department Of Physiology & Immunology School Of Medicine Konkuk University

• Cho S.

  Department Of Physiology And Anesthesiology College Of Medicine Institute Of Biomedical Science And

• Kim Junghwan

  Dep. Of Physical Therapy Coll. Of Public Health & Welfare Yongin Univ.

• KIM Bokyung

  Department of Medicine, Konkuk University

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