サイクリックAMPによる食細胞の活性酸素産生抑制機構  [in Japanese] 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^<2+>influx  [in Japanese]

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Abstract

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 E<SUB>1</SUB> combined with a cAMP-phosphodiesterase inhibitor. Increasing cAMP was also inhibitory to fMLP-induced activation of phosphatidylinositol (PI) 3-kinase and Ca<SUP>2+</SUP> 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 Ca<SUP>2+</SUP> 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 Ca<SUP>2+</SUP> uptake was prevented. The chemotactic peptide activated PI 3-kinase even in cells in which the receptormediated intracellular Ca<SUP>2+</SUP> mobilization and respiratory burst were both abolished by exposure of the cells to a permeable Ca<SUP>2+</SUP> chelating agent. Thus, stimulation of fMLP receptors gave rise to dual effects, activation of PI 3-kinase and intracellular Ca<SUP>2+</SUP> 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.

Journal

  • Folia Pharmacologica Japonica

    Folia Pharmacologica Japonica 106, 132-137, 1995-09-01

    The Japanese Pharmacological Society

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