PMID: 8614265Jan 1, 1996Paper

Potent inhibition of the inducible isoform of nitric oxide synthase by aminoethylisoselenourea and related compounds

Life Sciences
G J SouthanC Szabo

Abstract

The generation of nitric oxide (NO) by nitric oxide synthase (NOS) can be inhibited by certain guanidines and S-alkylisothioureas. In particular, aminoethylisothiourea (AE-TU) shows selectivity towards the inducible isoform (iNOS) over the endothelial isoform (ecNOS). Here we report on the effects of the selenium analog of AE-TU, aminoethylisoselenourea (AE-SeU), and its homologue, aminopropylisoselenourea (AP-SeU), on the activities of iNOS and ecNOS. AE-SeU and AP-SeU inhibited the conversion of L-arginine to L-citrulline in homogenates of lung taken from endotoxin-treated rats (a model of iNOS acitivity) with potencies (EC50=1.1, and 0.1 microM, respectively) greater than that of N(G)-methyl-L-arginine (L-NMA) (22 microM). In contrast, AE-SeU and AP-SeU were weaker than or similar to L-NMA at inhibiting ecNOS activity in homogenized bovine endothelial cells (EC50 values = 104, 15, and 16 microM, respectively). AE-SeU and AP-SeU potently inhibited nitrite formation by immunostimulated J774 macrophages (a model of iNOS activity) with EC50 values of 10 and 4 microM respectively. The corresponding EC50 value for L-NMA was 160 microM. The inhibition was dose-dependently reduced by increasing concentrations of L-arginine in the me...Continue Reading

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Citations

Jan 1, 1997·Life Sciences·R B MuijsersF P Nijkamp
Feb 19, 1999·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·G Sadeghi-HashjinF P Nijkamp
May 20, 1998·Archives of Physiology and Biochemistry·B P KangM P Bansal
May 30, 2001·Biochemical Pharmacology·B BillackJ D Laskin

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