S-nitrosoglutathione breakdown prevents airway smooth muscle relaxation in the guinea pig
S-nitrosoglutathione breakdown prevents airway smooth muscle relaxation in the guinea pig
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DOI：
10.1152/ajplung.2000.279.4.l716
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发表时间：
2000-10-01
影响因子：
4.9
通讯作者：
Gaston, B
中科院分区：
文献类型：
--
作者：
Fang, KH;Johns, R;Gaston, B
内源性支气管扩张剂S-亚硝基谷胱甘肽（GSNO）在几乎致命的哮喘儿童气道水平较低。我们假设GSNO可以在肺中被分解，并且这种催化剂可以抑制气道平滑肌松弛。在我们的实验中，GSNO被豚鼠肺匀浆分解，特别是在卵清蛋白致敏（OS）后。两种肺蛋白组分具有分解代谢活性。一个是NADPH依赖性的，OS后更活跃，另一个是NADPH非依赖性的，部分被金硫葡萄糖抑制。具有GSNO分解代谢活性的豚鼠肺组织蛋白组分抑制GSNO介导的豚鼠气管环舒张。GSNO的舒张作用可被金硫葡萄糖部分恢复。这些观察结果表明，豚鼠中GSNO的催化作用1）由肺蛋白介导，2）在OS后部分上调，3）可能有助于增加气道平滑肌张力。我们推测，肺中GSNO的酶分解可能通过抑制GSNO的有益作用（包括其对气道平滑肌张力的作用）而导致哮喘病理生理学。
Airway levels of the endogenous bronchodilator S-nitrosoglutathione (GSNO) are low in children with near-fatal asthma. We hypothesized that GSNO could be broken down in the lung and that this catabolism could inhibit airway smooth muscle relaxation. In our experiments, GSNO was broken down by guinea pig lung homogenates, particularly after ovalbumin sensitization (OS). Two lung protein fractions had catabolic activity. One was NADPH dependent and was more active after OS. The other was NADPH independent and was partially inhibited by aurothioglucose. Guinea pig lung tissue protein fractions with GSNO catabolic activity inhibited GSNO-mediated guinea pig tracheal ring relaxation. The relaxant effect of GSNO was partially restored by aurothioglucose. These observations suggest that catabolism of GSNO in the guinea pig 1) is mediated by lung proteins, 2) is partially upregulated after OS, and 3) may contribute to increased airway smooth muscle tone. We speculate that enzymatic breakdown of GSNO in the lung could contribute to asthma pathophysiology by inhibiting the beneficial effects of GSNO, including its effect on airway smooth muscle tone.