A novel mechanism of soluble guanylate cyclase stimulation: time-dependent activation by bacterial lipopolysaccharide in rat fetal spleen cells.
A novel mechanism of soluble guanylate cyclase stimulation: time-dependent activation by bacterial lipopolysaccharide in rat fetal spleen cells.
复制标题
可溶性鸟苷酸环化酶刺激的新机制：细菌脂多糖在大鼠胎儿脾细胞中的时间依赖性激活。
DOI：
10.1016/0167-4889(88)90209-1
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Gerzer,R
中科院分区：
文献类型：
--
作者：
Graber,SE;Clancey,MA;Wells,JN;Gerzer,R
少量的细菌脂多糖（LPS）以剂量和时间依赖的方式极大地增加了大鼠胎肝和脾细胞短期培养物中的cGMP水平。为了确定鸟苷酸环化酶在这种反应中的作用，使用完整或破碎的胎儿脾细胞（迄今为止评估的最敏感的组织）进行了一系列实验。即使在最大剂量的 LPS 下，磷酸二酯酶抑制剂 1-甲基-3-异丁基黄嘌呤也能增强这些细胞培养物中的 LPS-cGMP 效应。此外，将完整细胞与LPS孵育4小时后，可溶性鸟苷酸环化酶(EC 4.6.1.2)活性增加了2倍，而颗粒活性没有变化。可溶性活性的增加与LPS的剂量成正比，与cGMP水平的升高同步，并且与cGMP-磷酸二酯酶(EC 3.1.4.17)活性的任何变化无关。与完整细胞相比，通过向脾细胞中添加LPS，总的或可溶性鸟苷酸环化酶活性均未增加，总胞质在10分钟至3.5小时的不同时间也没有增加。这些结果表明，LPS-cGMP 反应是由于可溶性鸟苷酸环化酶活性的持续间接刺激所致，该活性具有剂量和时间依赖性。
Small amounts of bacterial lipopolysaccharide (LPS) greatly increase cGMP levels in short term cultures of rat fetal liver and spleen cells in a dose and time dependent manner. To determine the role of guanylate cyclase in this response, a series of experiments was undertaken using either intact or broken fetal spleen cells, the most sensitive tissue evaluated to date. The phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine, potentiated the LPS-cGMP effect in cultures of these cells even at maximal doses of LPS. Moreover, after incubation of intact cells with LPS for 4 h, soluble guanylate cyclase (EC 4.6.1.2) activity was increased 2-fold, whereas particulate activity was unchanged. This increase in soluble activity was proportional to the dose of LPS, was synchronous with the elevation of cGMP levels, and was not associated with any change in cGMP-phosphodiesterase (EC 3.1.4.17) activity. In contrast to intact cells, neither total nor soluble guanylate cyclase activity was increased by the addition of LPS to spleen cells, neither total cytosol for various times from 10 min to 3.5 h. These results suggest that the LPS-cGMP response is due to a persistent indirect stimulation of soluble guanylate cyclase activity that is both dose and time dependent.