[Highly selective inhibition of inducible nitric oxide synthase in vitro by a tripeptide as a new arginine analog].
OBJECTIVE
To investigate the inhibitory effect of a tripeptide, a new arginine analog, on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS).


METHODS
Macrophages challenged with lipopolysaccharide were cultured to test the inhibitory effect of the arginine analog of different concentrations on iNOS. Primarily cultured human umbilical vein endothelial cells (HUVECs) treated with insulin were used to test the effect of the analog on endothelial NOS (eNOS).


RESULTS
The new arginine analog significantly inhibited NO production in the macrophages in a dose-dependent manner, but had little effect on insulin-stimulated NO production in HUVECs. The new analog could significantly suppress iNOS activity, but had no significant inhibitory effect on constitutive NOS activity or eNOS activity. Western blot analysis showed that the new analog did not significantly affect the protein expression of iNOS.


CONCLUSIONS
The new analog is a NOS inhibitor with high selectivity on iNOS.
Sun
Fei
F
Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. sunfei@fimmu.com
Wu
Sai-zhu
SZ
Zhang
Xiao-tian
XT
Liu
Chang-qing
CQ
D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*
D007328:Insulin; D008070:Lipopolysaccharides; D009842:Oligopeptides; D009569:Nitric Oxide; D001120:Arginine; D052247:Nitric Oxide Synthase Type II