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- Material Type
- 文書・図像類
- Author/Editor
- 永山, 哲也
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- Alternative Title
- C-type natriuretic peptide modulates permeability of the blood; brain barrier
- Text Language Code
- jpn
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- Target Audience
- 一般
- Note (General)
- 2011-2013年度科学研究費助成事業（基盤研究（C））研究成果報告書 課題番号：23592100 研究代表者：永山哲也（鹿児島大学・医歯（薬）学総合研究科・客員研究員）C型ナトリウム利尿ペプチド（CNP）は、脳に豊富に存在することが報告されているが、血液脳関門（BBB）に対する機能は明らかではない。本研究では、CNPによるBBB透過性亢進作用とそのメカニズムを解明した。BBBのバリア機能は、CNPの濃度依存的に減少した。CNPの作用は、cGMPのアナログである8-Br-cGMPで再現され、PKGの阻害剤であるRp-8-CPT-cGMPで阻害された。さらに、マウスにCNPを静注すると、血中フルオロセインの脳実質移行性が増加した。以上の結果より、CNPはBBBの透過性を亢進することが可能で、この結果は脳に対するドラッグデリバリーシステムの構築に寄与できる。C-type natriuretic peptide (CNP) is abundant in brain, but its effect on blood-brain barrier (BBB) permeability has not been clarified yet. Here, we examined this effect. Transendothelial electrical resistance (TEER) of in vitro BBB model, was significantly dose dependently decreased by CNP. CNP treatment reduced both the messenger RNA and protein expressions of zonula occludens-1 (Z0-1). The effects on TEER, mRNA, and protein expressions of ZO-1 were mimicked by cyclic GMP (cGMP) analog 8-bromo-cGMP and reversed by protein kinase G (PKG) inhibitor Rp-8-CPT-cGMPS, thus implying the role of PKG and cGMP signaling in BBB function. In vivo study of mouse brain by fluorimetric analysis with intravenous administration of sodium fluorescein also showed a significant increase in BBB permeability by CNP. These findings suggest that CNP modulates the BBB permeability by altering ZO-1.