Comparison of the inhibitory effect of isothiourea and mercaptoalkylguanidine derivatives on the alternative pathways of arginine metabolism in macrophages

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• 作者：Hrab&aacute ; k ; Andr&aacute ; s ; Bajor ; Tam&aacute ; s ; Southan ; Garry J. ; Salzman ; Andrew L. ; et. al.
• 关键词：nitric oxide ; nitric oxide synthases ; isothiourea ; mercapto-alkylguanides ; macrophages ; arginase
• 刊名：Life Sciences
• 出版年：1997
• 期刊代码：62_00243205
• 类别：imm
• 出版时间：May 23, 1997
• 卷：60
• 期：26
• 页码：PL395-PL401
• 文件大小：385 K

摘要

Novel, non-arginine based compounds have been identified as potent inhibitors of nitric oxide synthase (NOS). Members of the isothiourea and mercaptoalkylguanidine classes have generated much interest, as some members of these classes show selectivity towards the inducible isoform of NOS (iNOS), which plays a role in inflammation and shock. Here we compared the effect of a number of these compounds as well as L-arginine based NOS inhibitor reference compounds on macrophage-derived and liver arginase and macrophage iNOS activities. From the non-arginine based NOS inhibitors studied only S-aminoethyl-isothiourea (AETU) caused a slight inhibition of arginase activity. This inhibition was kinetically competitive and due to the rearrangement of AETU to mercapto-ethylguanidine (MEG). The weak inhibitory effect of non-arginine based iNOS inhibitors on arginase activity further supports the view that such compounds may be of practical use for inhibition of NO production in cells simultaneously expressing iNOS and arginase.