Inhibition of Nitric Oxide Production and Protein Tyrosine Nitration Contribute to Neuroprotection by a Novel Calmodulin Antagonist, DY-9760e, in the Rat Microsphere Embolism(Pharmacology)

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概要

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• Microsphere embolism (ME)-induced ischemia model in rat resembles to multiple brain embolism in human with several clinical features. We here tested whether nitric oxide (NO) production contributes to the neuronal injury in the ME model. A novel calmodulin antagonist, DY-9760e, having a potent inhibitory effect on neuronal nitric oxide synthase (nNOS), reduced brain infarct size in the ME-induced brain ischemia. Consistent with our previous observation with gerbil ischemia/reperfusion model, DY-9760e completely inhibited NO production immediately after and 24 or 48h after ME. Unlike the gerbil ischemia/reperfusion model, protein tyrosine nitration markedly increased 6-48h after ME. DY-9760e treatment completely inhibited the marked increase in the protein tyrosine nitration at 24h after ME. These results suggest that the inhibition of NO production and protein tyrosine nitration by DY-9760e contribute to its neuroprotective action in the ME-induced brain damage.

• 公益社団法人日本薬学会の論文
• 2005-09-01

著者

• Fukunaga Kohji

  Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan

• Shirakura Takashi

  Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Tohoku University

• HAN Feng

  Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine

• Han Feng

  Inst. Of Pharmacology & Toxicology And Biochemical Pharmaceutics Coll. Of Pharmaceutical Science

• Han Feng

  Department Of Chemistry University Of Rhode Island

• KASAHARA Jiro

  Department of Mechanical Systems Engineering, Muroran Institute of Technology

• Fukunaga Kohji

  Tohoku Univ. 21st Century Coe Program “crescendo" Jpn

• Fukunaga K

  Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Tohoku University

• Fukunaga Kohji

  Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Tohoku University

• SHIOTA Norifumi

  Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University

• MORIGUCHI Shigeki

  Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University

• SATO Toshiyuki

  New Product Research Laboratories II, Daiichi Pharmaceutical Co., Ltd.

• SHIRASAKI Yasufumi

  New Product Research Laboratories II, Daiichi Pharmaceutical Co., Ltd.

• Kasahara Jiro

  Department Of Pharmacology Tohoku University Graduate School Of Pharmaceutical Sciences

• Kasahara Jiro

  Department Of Aerospace Engineering Nagoya University

• Shiota Norifumi

  Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Tohoku University

• Moriguchi Shigeki

  Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Tohoku University

• Shirasaki Yasufumi

  New Product Research Laboratories Ii Daiichi Pharmaceutical Co. Ltd.

• Shirasaki Yasufumi

  New Product Research Laboratories Ii Daiichi Pharmaceutical

• Sato Toshiyuki

  New Product Research Laboratories Ii Daiichi Pharmaceutical Co. Ltd.

• Moriguchi Shigeki

  Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School:Department of Pharmacology, Tohoku University Graduate School of Pharmaceutical Sciences

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