グリベンクラミドは,アデノシンA1受容体媒介の心臓保護を阻害し,麻痺した犬の心筋に作用する
1Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Circulation
|July 1, 1993
まとめ
アデノシンA1受容体を刺激することで,血流の繰り返し阻害によって引き起こされる麻痺から心臓を保護します. この保護効果はATP依存性Kチャネル (KATP) を含む可能性があり,不全性心疾患の潜在的な治療標的を示唆する.
科学分野:
- 心臓病学 心臓病学
- 薬理学 薬理学とは
- 生理学 生理学とは
背景:
- 心筋麻痺は,後発血性機能不全である.
- アデノシン受容体は,イシュケミア中の心臓機能に役割を果たします.
- 特定のアデノシン受容体のサブタイプと,麻酔におけるKATPチャネルとの相互作用は不明である.
研究 の 目的:
- 繰り返しの冠動脈閉塞に伴う心筋麻痺におけるアデノシンの役割を調査する.
- 特定のアデノシン受容体亜型 (A1またはA2) を特定するために.
- アデノシンA1受容体とATP依存性Kチャンネル (KATP) の相互作用を検証する.
主な方法:
- 繰り返し冠動脈の閉塞と再注射を受けた麻酔を受けた犬で研究が行われました.
- 地域的な心臓機能は,ソノミクロメトリーを用いて評価された.
- 選択的なアデノシンA1受容体アゴニスト (CPA) とアンタゴニスト (DPCPX),A2受容体アゴニスト (CGS 21680),KATPチャネルブロッカー (グリベンクラミド) が投与されました.
主要な成果:
- CPA投与は心臓機能の回復を改善したが,DPCPXは回復を悪化させた.
- アデノシンA2受容体アゴニストであるCGS 21680は有意な効果を示さなかった.
- グリベンクラミドはCPAの保護効果をなくし,KATPチャネルの関与を示した.
結論:
- 心筋アデノシンA1受容体刺激は,特にイシュケミアの初期に,繰り返される閉塞に対する心臓保護を提供します.
- この心臓保護は部分的にグリベンクラミドに敏感なメカニズムによって媒介され,おそらくKATPチャネル開通を伴うようです.
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