アゴニスト誘発のCa2+シグナリングパターンのNAADPによる協調は,臓のアシナ細胞におけるNAADPによる
J M Cancela1, G C Churchill, A Galione
1Department of Pharmacology, University of Oxford, UK. j.m.cancela@liverpool.ac.uk
Nature
|March 17, 1999
まとめ
ニコチン酸アデニン・ディヌクレオチド・リン酸塩 (NAADP) は,他のメッセンジャーとは異なり,臓細胞で多様なカルシウム信号を誘発する. これはNAADPが哺乳類における新たな細胞内伝達物質として作用することを示唆している.
科学分野:
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
- 生理学 生理学とは
背景:
- ホルモンや神経伝達物質は,細胞内カルシウム (Ca2+) の放出を調節し,特定のシグナリングパターンを生み出します.
- イノシトール三酸 (InsP3) とサイクルアデノシン5'-二酸リボース (cADPR) は,それぞれInsP3とライオノジン受容体を活性化するCa2+メッセンジャーとして知られています.
- 既存のメッセンジャーは,臓のアシナ細胞におけるコレシストキニン (CCK) によって誘発されるCa2+シグナリングの複雑性を完全に説明できません.
研究 の 目的:
- ニコチン酸アデニン・ディヌクレオチド・リン酸塩 (NAADP) が,臓のアシナ細胞における潜在的なCa2+メッセンジャーとしての役割を調査する.
- NAADPのCa2+動員効果をInsP3およびcADPRと比較する.
- CCKが誘発するCa2+信号を調節するメカニズムを解明する.
主な方法:
- 臓のアシナ細胞における細胞内Ca2+濃度の測定.
- NAADP,cADPR,InsP3を適用してCa2+の放出を刺激する.
- 異なるNAADP濃度を使用して,CCKによって誘発されるCa2+信号の選択的不活性化.
主要な成果:
- NAADPは,InsP3とcADPRとは異なる,短期間および長期にわたるスパイクを含む,さまざまなCa2+反応を誘発しました.
- 臓のアシナ細胞は,cADPRやInsP3.3と比較してNAADPに対してより高い感受性を示した.
- 高濃度のNAADPは,CCK誘発のCa2+シグナリングを選択的に抑制した.
結論:
- NAADPは,臓のアシナ細胞における強力なCa2+動員メッセンジャーとして機能する.
- NAADP媒介のシグナル伝達はInsP3とcADPR経路とは異なり,それらを調節することができる.
- NAADPは,哺乳類の細胞信号伝達に潜在的に関与する新しい細胞内伝達物質を表しています.
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