REQUIREMENT OF THIOLS FOR ACTIVATION OF CORONARY ARTERIAL GUANYLATE-CYCLASE BY GLYCERYL TRINITRATE AND SODIUM-NITRITE - POSSIBLE INVOLVEMENT OF S-NITROSOTHIOLS
REQUIREMENT OF THIOLS FOR ACTIVATION OF CORONARY ARTERIAL GUANYLATE-CYCLASE BY GLYCERYL TRINITRATE AND SODIUM-NITRITE - POSSIBLE INVOLVEMENT OF S-NITROSOTHIOLS
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DOI：
10.1016/0304-4165(80)90297-4
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发表时间：
1980-01-01
期刊：
影响因子：
--
通讯作者：
GRUETTER, CA
中科院分区：
文献类型：
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作者：
IGNARRO, LJ;GRUETTER, CA
三硝酸甘油酯特别需要半胱氨酸，但浓度 < 10 mM 的 NaNO2 需要几种硫醇或抗坏血酸中的一种，才能激活牛冠状动脉的可溶性鸟苷酸环化酶。硝普盐或一氧化氮激活鸟苷酸环化酶不需要添加硫醇或抗坏血酸。各种硫醇增强硝普盐的活化，但没有一种硫醇测试增强一氧化氮的活化。 S-亚硝基半胱氨酸是半胱氨酸与 NO2- 或一氧化氮反应时形成的，是鸟苷酸环化酶的有效激活剂。同样，微摩尔浓度的青霉胺、GSH [谷胱甘肽]和二硫苏糖醇的 S-亚硝基衍生物（通过硫醇与一氧化氮反应制备）可激活鸟苷酸环化酶。 S-亚硝基硫醇对鸟苷酸环化酶的激活与一氧化氮和硝普钠的激活相似，因为激活被高铁血红蛋白、铁氰化物和亚甲蓝抑制。类似地，三硝酸甘油加半胱氨酸和NaNO2加硫醇或抗坏血酸盐对鸟苷酸环化酶的激活被高铁血红蛋白、铁氰化物和亚甲蓝抑制。每种测试的化合物对鸟苷酸环化酶的激活可能通过共同的机制发生，可能涉及一氧化氮。 S-亚硝基硫醇可以作为三硝酸甘油酯、NaNO2 和可能的硝普盐激活鸟苷酸环化酶的中间体。
Glyceryl trinitrate specifically required cysteine, but NaNO2 at concentrations < 10 mM required 1 of several thiols or ascorbate, to activate soluble guanylate cyclase from bovine coronary artery. Guanylate cyclase activation by nitroprusside or nitric oxide did not require the addition of thiols or ascorbate. Various thiols enhanced activation by nitroprusside, none of the thiols tested enhanced activation by nitric oxide. S-Nitrosocysteine, which is formed when cysteine reacts with NO2- or nitric oxide, was a potent activator of guanylate cyclase. Similarly, micromolar concentrations of the S-nitroso derivatives of penicillamine, GSH [glutathione] and dithiothreitol, prepared by reacting the thiol with nitric oxide, activated guanylate cyclase. Guanylate cyclase activation by S-nitrosothiols resembled that by nitric oxide and nitroprusside in that activation was inhibited by methemoglobin, ferricyanide and methylene blue. Similarly, guanylate cyclase activation by glyceryl trinitrate plus cysteine and by NaNO2 plus a thiol or ascorbate, was inhibited by methemoglobin, ferricyanide and methylene blue. The activation of guanylate cyclase by each of the compounds tested may occur through a common mechanism, perhaps involving nitric oxide. S-Nitrosothiols could act as intermediates in the activation of guanylate cyclase by glyceryl trinitrate, NaNO2 and possibly nitroprusside.