動脈硬化症のウサギの冠動脈の5-ヒドロキシトリプタミン1B受容体を通じたセロトニン誘発の超収縮
T Ishida1, S Kawashima, Hirata Ki
1First Department of Internal Medicine and Institute for Experimental Animals, Kobe (Japan) University School of Medicine.
Circulation
|March 10, 2001
まとめ
動脈硬化症は,ウサギの冠動脈におけるセロトニン誘発の収縮を増加させ,主に上調された5-HT ((1B) 受容体を通じます. このメカニズムは,カルシウムの動員を強化し,心筋動脈不全症に寄与します.
科学分野:
- 心血管生物学 心血管生物学
- 薬理学 薬理学とは
- 動脈硬化症の研究 動脈硬化症の研究
背景:
- 動脈硬化性血管におけるセロトニン (5-ヒドロキシトリプタミン [5-HT]) に対する血管収縮の増大は,心筋不全症に寄与する.
- 動脈硬化症のウサギの冠動脈におけるセロトニン誘発の超収縮の背後にあるメカニズムが調査されました.
研究 の 目的:
- 動脈硬化性冠動脈におけるセロトニン誘発性血管収縮の強化に起因するメカニズムを解明する.
- この超収縮に関与する特定のセロトニン受容体のサブタイプとシグナル伝達経路を特定する.
主な方法:
- コントロールおよびワタナベ遺伝性多脂症 (WHHL) のウサギのエンドテリアが脱皮した冠動脈におけるセロトナーギー薬に対する収縮反応を調べた.
- 5-HT(1B/1D) と5-HT(2) 受容体抗体, pertussis toxin を利用し,細胞内カルシウム ([Ca(2+) ](i)) とmRNAレベルを測定しました.
主要な成果:
- WHHL冠動脈は,より低い値濃度と最大応答の増加で,5-HT(1) -受容体アゴニストに対する高収縮を示した.
- セロトニン誘発の収縮は,5-HT (((1B/1D)) 反抗体と pertussis毒素によって抑制されたが,5-HT (((2) 反抗体によって抑制されなかった.
- 増加した[Ca2+]上昇と相関する超収縮,および5-HT1B) mRNAレベルはWHHL動脈で著しく上調されました.
結論:
- 動脈硬化ウサギの冠動脈は,セロトニンに対する反応として,収縮とカルシウム動員が強化されている.
- 動脈硬化で上位調節される5HT1B受容体は,セロトニンの増強効果の媒介者である可能性が高い.
- これらの発見は,動脈硬化症中のセロトニン媒介性血管収縮における5-HT (((1B)) 受容体のアップレギュレーションの役割を強調しています.
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