Nitroglycerin metabolism in vascular tissue: role of glutathione S-transferases and relationship between NO. and NO2- formation.
Nitroglycerin metabolism in vascular tissue: role of glutathione S-transferases and relationship between NO. and NO2- formation.
复制标题
血管组织中的硝酸甘油代谢：谷胱甘肽 S-转移酶的作用和 NO 之间的关系。
DOI：
10.1042/bj2920545
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Harrison,DG
中科院分区：
文献类型：
--
作者：
Kurz,MA;Boyer,TD;Whalen,R;Peterson,TE;Harrison,DG
硝酸甘油是一种常用的药物，它通过释放一氧化氮（NO）来产生血管舒张。硝酸甘油释放一氧化氮的机制。仍未定义。最近，谷胱甘肽s -转移酶被认为是这一过程的重要贡献者。已知它们从硝酸甘油中释放NO2-，但尚未显示释放NO。本研究旨在研究内源性谷胱甘肽s -转移酶在这一代谢过程中的作用。将狗颈动脉匀浆与硝酸甘油、NO进行无氧孵育。化学发光法测定NO2-产率。研究了谷胱甘肽s -转移酶的作用，用硝酸甘油孵育匀浆，在1 mM谷胱甘肽谷胱甘肽s -转移酶抑制剂GSH或1 mM s -己基谷胱甘肽存在下。匀浆释放163 pmol NO。/h / mg硝酸甘油蛋白和2370 pmol NO2-/h / mg。产量提高82%，二氧化氮产量提高98%。s -己基谷胱甘肽抑制谷胱甘肽s -转移酶活性96%，降低NO2-产量78%，但对no无影响。释放。谷胱甘肽s -转移酶活性与NO2生成呈线性关系，而谷胱甘肽s -转移酶活性与NO生成呈线性关系。释放是不相关的。Western-blot分析表明，狗颈动脉血管平滑肌中含有Pi和Mu形式的谷胱甘肽s转移酶，且以Pi和Mu形式的谷胱甘肽s转移酶为主。纯化的人Pi和大鼠Mu异构体只将硝酸甘油代谢为NO2-，而不代谢为NO。基于这些发现，我们得出结论：(1)谷胱甘肽s -转移酶不参与硝化甘油向NO的生物转化。，而是作为硝化甘油的降解途径；(2)释放NO。硝酸甘油的生成不依赖于NO2-的生成。
Nitroglycerin is a commonly employed pharmacological agent which produces vasodilatation by release of nitric oxide (NO.). The mechanism by which nitroglycerin releases NO. remains undefined. Recently, glutathione S-transferases have been implicated as important contributors to this process. They are known to release NO2- from nitroglycerin, but have not been shown to release NO.. The present studies were designed to examine the role of endogenous glutathione S-transferases in this metabolic process. Homogenates of dog carotid artery were incubated anaerobically with nitroglycerin, and NO. and NO2- production was determined by chemiluminescence. The role of glutathione S-transferases was studied by incubating homogenates with nitroglycerin in the presence of 1 mM GSH or 1 mM S-hexyl-glutathione, a potent inhibitor of glutathione S-transferases. Homogenates released 163 pmol of NO./h per mg of protein from nitroglycerin, and 2370 pmol of NO2-/h per mg. Adding GSH decreased NO. production by 82% and increased NO2- production by 98%. S-Hexylglutathione inhibited glutathione S-transferase activity by 96% and decreased NO2- production by 78%, but had no effect on NO. release. A linear relationship between glutathione S-transferase activity and NO2- production was observed, whereas glutathione S-transferase activity and NO. release were unrelated. Western-blot analysis demonstrated that dog carotid vascular smooth muscle contained Pi and Mu forms of glutathione S-transferases, with a predominance of the former. Purified preparations of human Pi and rat Mu isoforms metabolized nitroglycerin only to NO2- and not to NO.. On the basis of these findings, we conclude that (1) glutathione S-transferases do not contribute to the bioconversion of nitroglycerin to NO., but instead act as a degradative pathway for nitroglycerin, and (2) the release of NO. from nitroglycerin is not dependent on the formation of NO2-.