Physiology and Pathophysiology of Proteinase-Activated Receptors (PARs) : Role of Tryptase/PAR-2 in Vascular Endothelial Barrier Function
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概要
- 論文の詳細を見る
Proteinase-activated receptor-2 (PAR-2) plays important roles in a variety of pathophysiological functions, including inflammatory responses and nociception. In this minireview, we describe the role of PAR-2 in acute inflammatory responses in lungs associated with iodinated radiographic contrast medium (RCM). Intravenous injection of RCM to rats induces lung injury characterized by vascular hyperpermeability, edema, and respiratory depression. Nafamostat, which is found to be the most potent and specific tryptase inhibitor, prevents RCM-induced lung injury. In cultured endothelial cells of human pulmonary artery and bovine aorta, RCM, when applied in combination with mast cells, disrupts barrier function evaluated by the permeability of Evans blue through a monolayer of cultured cells, which is blocked by nafamostat and mimicked by tryptase and PAR-2 activating peptide. The tryptase-induced barrier dysfunction is blocked completely by a phospholipase C inhibitor and partially inhibited by a IP3 receptor blocker, protein kinase C inhibitor, or Rho kinase inhibitor. Morphological observations reveal the formation of actin stress fibers and disappearance of the intercellular meshwork structure of vascular endothelial-cadherin after application of RCM or PAR-2 ligands. Therefore, the release of mast cell tryptase and subsequent activation of endothelial PAR-2 are involved in acute lung injury induced by RCM.
- 社団法人 日本薬理学会の論文
- 2005-01-20
著者
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Oishi Ryozo
Department of Pharmacy, Kyushu University Hospital
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Sendo Toshiaki
Dep. Of Hospital Pharmacy Okayama Univ. Medical School Jpn
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Sendo Toshiaki
岡山大学 医歯薬学総合研究科薬理学
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Sendo Toshiaki
Department Of Hospital Pharmacy Okayama University Medical And Dental School
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Sendoh Toshiaki
九州大学 薬
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Sendo T
Department Of Hospital Pharmacy Faculty Of Medicine Kyushu University
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Sendo Toshiaki
Department Of Hospital Pharmacy Faculty Of Medicine Kyushu University
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Oishi R
Dep. Of Pharmacy Kyushu Univ. Hospital Jpn
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Oishi Ryozo
Department Of Pharmacy Kyushu University Hospital
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Oishi Ryozo
Department Of Hospital Pharmacy Faculty Of Medicine Kyushu University
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Itoh Yoshinori
Department of Cardiovascular Medicine, Hokkaido University, Graduate School of Medicine
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Itoh Yoshinori
九州大学病院 薬剤部
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Itoh Yoshinori
Department Of Cardiovascular Medicine Hokkaidou University Graduate School Of Medicine
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Itoh Yoshinori
Department Of Cardiovascular Medicine Hokkaido University Graduate School Of Medicine
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Itoh Yoshinori
Department Of Cardiorenal And Cerebrovascular Medicine Kagawa University
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Sendo Toshiaki
Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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