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Studies on the mechanism for arachidonic acid liberation in mammalian cells with stimulus-response coupling

刺激-反应耦合哺乳动物细胞花生四烯酸释放机制研究

基本信息

批准号：
06672213
负责人：
SATO Takashi
金额：
$ 1.41万
依托单位：
Kyoto Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06672213/
关键词：
phospholipase A_2 phospholipase D arachidonic acid prostaglandin D_2 mast cell

项目摘要

Arachidonic acid as a precursor for eicosanoid is known to be liberated by the hydrolytic action of phospholipase A_2 (PLA_2) on membrane phospholipids. The present study has been undertaken to investigate whether or not the arachidonic acid liberation by diacylglycerol (DAG) lipase from DAG which is produced through the sequential actions of phospholipase D (PLD) and phosphatidate phosphohydrolase (PAPase), is the important pathway upon stimulation in rat peritoneal mast cells. The results obtained are as follows.1. The arachidonic acid liberation upon stimulation with Ca^<2+> ionophore ionomycin was inhibited by about 50 % by addition of ethanol to suppress phosphatidic acid production through PLD activation, or of inhibitors for PAPase or DAG lipase.2. The arachidonic acid liberation in response to IgE receptor-dependent stimulation was completely inhibited by ethanol or the inhibitors indicated above.3. The production of prostaglandin D_2 (PGD_2), a major metabolite of arachidonic acid in rat peritoneal mast cell in response to IgE receptor-dependent stimulation and also ionomycin, was completely suppressed by ethanol or the inhibitors indicated above.4. Stimulation with melittin, that can specifically activate PLA_2, induced arachidonic acid liberation but not PGD_2 production, while stimulation with ADP ribosylation factor (ARF), that does PLD,induced marked PGD_2 production as well as arachidonic acid liberation both of which were completely suppressed in the presence of ethanol.These results indicate that in rat peritoneal mast cells stimulus-induced arachidonic acid liberation is contributed by the sequential PLD/PAPase/DAG lipase pathway in addition to PLA_2 pathway, whereas PGD_2 production following arachidonic acid liberation is fully dependent on the PLD-linked lipid metabolism.

已知花生四烯酸作为类二十烷酸的前体，是通过磷脂酶 A_2 (PLA_2) 对膜磷脂的水解作用释放出来的。本研究旨在探讨磷脂酶 D (PLD) 和磷脂酸磷酸水解酶 (PAPase) 连续作用产生的二酰基甘油 (DAG) 脂肪酶从 DAG 中释放花生四烯酸是否是刺激大鼠腹膜肥大细胞的重要途径。得到的结果如下： 1．通过添加乙醇以通过PLD活化抑制磷脂酸产生，或添加PAP酶或DAG脂肪酶抑制剂，用Ca 2+ 离子载体离子霉素刺激时的花生四烯酸释放被抑制约50％。2．响应IgE受体依赖性刺激的花生四烯酸释放被乙醇或上述抑制剂完全抑制。3．前列腺素D_2（PGD_2）是大鼠腹膜肥大细胞中花生四烯酸的主要代谢物，响应IgE受体依赖性刺激和离子霉素的产生，被乙醇或上述抑制剂完全抑制。4．用蜂毒肽刺激，可以特异性激活PLA_2，诱导花生四烯酸释放，但不诱导花生四烯酸产生，而用ADP核糖基化因子（ARF）刺激，PLD，诱导显着的PGD_2产生以及花生四烯酸释放，在乙醇存在下，这两者都被完全抑制。这些结果表明，在大鼠腹膜肥大细胞中，刺激诱导花生四烯酸除 PLA_2 途径外，释放还由顺序的 PLD/PAPase/DAG 脂肪酶途径贡献，而花生四烯酸释放后的 PGD_2 产生完全依赖于 PLD 相关的脂质代谢。