サイクリックAMPによる食細胞の活性酸素産生抑制機構

• 櫨木 薫

  理化学研究所宇井特別研究室

• Ahmed Mosleh U.

  Ui Laboratory, the Institute of Physical and Chemical Research

• 櫨木 修

  東京大学薬学部生理化学教室

• 堅田 利明

  東京大学薬学部生理化学教室

• 宇井 理生

  理化学研究所宇井特別研究室

書誌事項

タイトル別名

• Cyclic AMP-increasing agents interfere with chemoattractant-induced respiratory burst in neutrophils as a result of the inhibition of phosphatidylinositol 3-kinase rather than receptor operated Ca<SUP>2+</SUP> influx

抄録

Superoxide anion and arachidonic acid were produced in guinea pig neutrophils in response to a chemotactic peptide (fMLP). Both responses were markedly, but the former response to a phorbol ester was not at all, inhibited when the cellular cAMP level was raised by prostaglandin E₁ combined with a cAMP-phosphodiesterase inhibitor. Increasing cAMP was also inhibitory to fMLP-induced activation of phosphatidylinositol (PI) 3-kinase and Ca²⁺ influx without any effect on the cation mobilization from intracellular stores. The fMLP-induced respiratory burst was abolished when PI 3-kinase was inhibited by wortmannin or LY294002, but was not affected when Ca²⁺ influx was inhibited. On the contrary, fMLP released arachidonic acid from the cells treated with the PI 3-kinase inhibitors as well as from non-treated cells, but it did not so when cellular Ca²⁺ uptake was prevented. The chemotactic peptide activated PI 3-kinase even in cells in which the receptormediated intracellular Ca²⁺ mobilization and respiratory burst were both abolished by exposure of the cells to a permeable Ca²⁺ chelating agent. Thus, stimulation of fMLP receptors gave rise to dual effects, activation of PI 3-kinase and intracellular Ca²⁺ mobilization; both effects were necessary for the fMLP-induced respiratory burst. Increasing cellular cAMP inhibited the respiratory burst and arachidonic acid release as a result of the inhibitions of PI 3-kinase and Ca2+ influx, respectively, in fMLP-treated neutrophils.

収録刊行物

• 日本薬理学雑誌

  日本薬理学雑誌 106 (supplement), 132-137, 1995

  公益社団法人 日本薬理学会

キーワード

• Pharmacology

詳細情報

• CRID: 1390282679247645312
• NII論文ID: 10008631372
• NII論文ID: 30034987127
• NII書誌ID: AN00198335
• DOI: 10.1254/fpj.106.supplement_132
• ISSN: 13478397
• ISSN: 00155691
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可