花生四烯酸动员激动剂在免疫系统细胞中诱导阿南达胺合成

Vasumati K. Pestonjamasp , Sumner H. Burstein
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引用次数: 114

摘要

药物动员花生四烯酸(AA)的能力可以预测巨噬细胞中anandamide (ANA)合成的增加。在RAW264.7小鼠巨噬细胞中,脂多糖(LPS)、血小板活化因子(PAF)和大麻素如Δ9-tetrahydrocannabinol (THC)、anandamide均为AA释放的激动剂,导致ANA合成增加。相比之下,一氧化氮刺激了AA的释放,但没有提高ANA的水平。ANA刺激自身合成表明存在正反馈机制。CB2受体可能参与thc介导的AA释放和ANA合成,使用拮抗剂SR144528。钙离子载体和吲哚美辛的结合也增加了ANA的合成,这表明ANA在该系统中是由环加氧酶代谢的。这些数据表明,ANA可能在免疫系统对大麻素和细菌内毒素的反应中发挥作用,并且AA动员是ANA合成增加的预测因子。
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Anandamide synthesis is induced by arachidonate mobilizing agonists in cells of the immune system

The hypothesis that the capability of agents to mobilize arachidonic acid (AA) could predict increased anandamide (ANA) synthesis in a macrophage cell line has been examined. Lipopolysaccharide (LPS), platelet-activating factor (PAF) and cannabinoids such as Δ9-tetrahydrocannabinol (THC) and anandamide were all found to be agonists for the release of AA and led to increased ANA synthesis in RAW264.7 mouse macrophage cells. Nitric oxide, in contrast, stimulated AA release without raising ANA levels. ANA stimulation of its own synthesis indicates the existence of a positive feedback mechanism. The possible involvement of the CB2 receptor in THC-mediated AA release and ANA synthesis is addressed using the antagonist SR144528. ANA synthesis is also increased by the combination of calcium ionophore and indomethacin, suggesting that ANA is metabolized by a cyclooxygenase in this system. The data imply that ANA could play a role in the response of the immune system to cannabinoids and bacterial endotoxins and that AA mobilization is a predictor for increased ANA synthesis.

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