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

András Hrabák, Tamás Bajor, Garry J. Southan, Andrew L. Salzman, Csaba Szabó

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)PL395-PL401
JournalLife Sciences
Volume60
Issue number26
DOIs
StatePublished - May 23 1997
Externally publishedYes

Keywords

  • Arginase
  • Isothiourea
  • Macrophage
  • Mercapto-alkylguanides
  • Nitric oxide
  • Nitric oxide synthase

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Biochemistry, Genetics and Molecular Biology

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