POSSIBLE INVOLVEMENT OF S-NITROSOTHIOLS IN THE ACTIVATION OF GUANYLATE-CYCLASE BY NITROSO-COMPOUNDS

POSSIBLE INVOLVEMENT OF S-NITROSOTHIOLS IN THE ACTIVATION OF GUANYLATE-CYCLASE BY NITROSO-COMPOUNDS
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DOI:
10.1016/0014-5793(80)80091-3
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发表时间:
1980-01-01
期刊:
影响因子:
3.5
通讯作者:
GRUETTER, CA
GRUETTER, CA
中科院分区:
生物学3区
文献类型:
--
作者:
IGNARRO, LJ;EDWARDS, JC;GRUETTER, CA

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高铁血红蛋白对一氧化氮(NO)、硝普苷和n -甲基-n '硝基-n -亚硝基胍(MNNG)激活冠状动脉可溶性鸟苷环化酶的抑制作用[11]。此外,二硫苏糖醇(DTT)增强了硝普苷和MNNG对冠状动脉和肝可溶性鸟苷酸环化酶的激活,而NO对其没有作用,并逆转了硝普苷和MNNG对高铁血红蛋白激活的阻断,而NO对其没有作用。事实上,DTT是硝普苷激活肝鸟苷酸环化酶所必需的。这些观察结果表明,DTT可能直接与亚硝基化合物反应,促进NO的释放,从而克服高铁血红蛋白的抑制[11]。DTT对鸟苷酸环化酶激活作用的另一种解释是,在硫代b存在的情况下,no部分从亚硝基化合物直接非酶转移到鸟苷酸环化酶(或铁血红素中间体)。以上每个假设都经过了检验,这里的数据表明:
The inhibitory effects of methemoglobin on activation of coronary arterial soluble guanylate cyclase by nitric oxide (NO), nitroprusside and N-methyl-N’nitro-N-nitrosoguanidine(MNNG) were described in [11. Also dithiothreitol (DTT) enhanced activation of coronary arterial and hepatic soluble guanylate cyclase by nitroprusside and MNNG but not by NO, and reversed the methemoglobin blockade of activation by nitroprusside and MNNG but not by NO. Indeed, DTT was required for hepatic guanylate cyclase activation by nitroprusside. These observations suggested that DTT may react directly with the nitroso compounds to promote release of NO, which may then overcome the inhibition by methemoglobin [11. An alternative explanation for the effects of DTT on guanylate cyclase activation was a direct nonenzymatic transfer of the NO-moiety from the nitroso compound to guanylate cyclase (or a ferroheme intermediate) in the presence of thioB. Each of the above hypotheses was tested and the data here illustrate that: