Involvement of neurokinin 1 receptors and the ligands in albumin permeability across endothelial cell monolayer

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462451
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: National Center for Global Health and Medicine (2015); 独立行政法人国立国際医療研究センター (2013)
• Principal Investigator: Azma Toshiharu 国立研究開発法人国立国際医療研究センター, その他部局等, その他 (60284197)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 血管内皮細胞 / 血管透過性 / ニューロキニン１受容体 / サブスタンスP / ヘモキニン / バリアント受容体

Outline of Final Research Achievements

This study was conducted to clarify the mechanisms for perioperative modulation of albumin permeability across endothelial cell monolayers. The expression of mRNA for full-length neurokinin-1 receptor NK1R in endothelial cells was confirmed although the level of expression was very low. The level of mRNA for truncated NK1R was much higher and constitutive. A NK1R ligand substance P (SP), failed to modulate the albumin permeability when it was solely applied, while it accelerated the permeability in combination with fresh frozen plasma (FFP). The increase in the albumin permeability by FFP was potently blocked by reagents with anti-thrombin activities (heparin or urinastatin). A NK1R antagonist Spantide reduced the FFP-provoked albumin permeability even in the absence of SP added. Endothelial cells expressed the mRNA for hemokinin (TAC4), indicating that hemokinin/NK1R pathway may be involved in the autocrine regulation for endothelial cell functions.

Free Research Field

周術期管理医学，麻酔科学，疼痛治療