Role of phosphodiesterases in the regulation of endothelial permeability in vitro.
Role of phosphodiesterases in the regulation of endothelial permeability in vitro.
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磷酸二酯酶在体外调节内皮细胞通透性中的作用。
DOI：
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发表时间：
1993
影响因子：
15.9
通讯作者：
C. Schudt
中科院分区：
文献类型：
--
作者：
Norbert Suttorp;U. Weber;T. Welsch;C. Schudt
中性粒细胞来源的过氧化氢（H2 O2）被认为在血管损伤和肺水肿的发病机制中起重要作用。H2 O2的时间和剂量依赖性增加的水力传导性和降低的选择性的内皮细胞单层来自猪肺动脉。用10（-12）M霍乱毒素或0.1 μ M毛喉素激活腺苷酸环化酶可完全抑制H2 O2对内皮通透性的影响。10（-8）M Sp-cAMPS，一种cAMP依赖性蛋白激酶A激动剂，具有类似的效果。磷酸二酯酶（PDE）抑制剂莫他苯宗（10（-4）M）、咯利普兰（10（-6）M）和扎达维林（10（-8）M）特异性抑制PDE同工酶III、IV和III/IV，当与10（-6）M前列腺素E1联合使用时，可有效阻断H2 O2诱导的内皮渗透性。总体细胞cAMP含量和抑制H2 O2对内皮细胞通透性的影响相关性较差。H2 O2暴露导致内皮细胞cAMP含量迅速大幅下降。PDE同工酶谱的分析表明，在猪肺内皮细胞的同工酶II，III和IV的高活性。这些数据表明，腺苷酸环化酶激活/PDE抑制是一个强大的方法来阻止过氧化氢诱导的内皮细胞通透性增加。当内皮细胞PDE同工酶谱和PDE抑制剂谱最佳匹配时，这一概念显得特别有价值。
Neutrophil-derived hydrogen peroxide (H2O2) is believed to play an important role in the pathogenesis of vascular injury and pulmonary edema. H2O2 time- and dose-dependently increased the hydraulic conductivity and decreased the selectivity of an endothelial cell monolayer derived from porcine pulmonary arteries. Effects of H2O2 on endothelial permeability were completely inhibited by adenylate cyclase activation with 10(-12) M cholera toxin or 0.1 microM forskolin. 10(-8) M Sp-cAMPS, a cAMP-dependent protein kinase A agonist, was similarly effective. The phosphodiesterase (PDE) inhibitors motapizone (10(-4) M), rolipram (10(-6) M), and zardaverine (10(-8) M), which specifically inhibit PDE-isoenzymes III, IV, and III/IV potently blocked H2O2-induced endothelial permeability when combined with 10(-6) M prostaglandin E1. Overall cellular cAMP content and inhibition of H2O2 effects on endothelial permeability were poorly correlated. H2O2 exposure resulted in a rapid and substantial decrease in endothelial cAMP content. The analysis of the PDE isoenzyme spectrum showed high activities of isoenzymes II, III, and IV in porcine pulmonary endothelial cells. The data suggest that adenylate cyclase activation/PDE inhibition is a powerful approach to block H2O2-induced increase in endothelial permeability. This concept appears especially valuable when endothelial PDE isoenzyme pattern and PDE inhibitor profile are matched optimally.
DOI：
10.1016/s0021-9258(19)77928-9
发表时间：
1988-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
P. Hyslop;Daniel;Hinshawz;Wayne A. Halsey;Ingrid;Schraufstatter;Richard D. Sauerhebery;Roger G. Spraggj;Janis H. Jackson;C G Cochrane
通讯作者：
P. Hyslop;Daniel;Hinshawz;Wayne A. Halsey;Ingrid;Schraufstatter;Richard D. Sauerhebery;Roger G. Spraggj;Janis H. Jackson;C G Cochrane
影响因子：
15.9
作者：
SCHRAUFSTATTER, IU;HINSHAW, DB;COCHRANE, CG
通讯作者：
COCHRANE, CG