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

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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
JournalLife Sciences
Volume60
Issue number26
DOIs
Publication statusPublished - May 23 1997

Fingerprint

Arginase
Macrophages
Metabolism
Nitric Oxide Synthase
Arginine
Protein Isoforms
Derivatives
Nitric Oxide Synthase Type II
Liver
Shock
Inflammation

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Comparison of the inhibitory effect of isothiourea and mercaptoalkylguanidine derivatives on the alternative pathways of arginine metabolism in macrophages. / Hrabák, A.; Bajor, Tamás; Southan, Garry J.; Salzman, Andrew L.; Szabó, Csaba.

In: Life Sciences, Vol. 60, No. 26, 23.05.1997.

Research output: Contribution to journalArticle

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