Polyamines inhibit lipopolysaccharide-induced nitric oxide synthase activity in rat liver cytosol

Liver cells can produce nitric oxide from L-arginine through either constitutive NO synthase or inducible NO synthase (NOS) detected after in vivo or in vitro treatment with cytokines and/or lipopolysaccharide (LPS). The effects of NO on liver cells are associated with protein synthesis and mitochondrial electron transfer inhibition. L-Arginine is also the precursor of L-ornithine and polyamines. The latter are considered to be protective in the liver in several experimental models. The aim of the present work was to test the effects of polyamines on LPS-inducible NOS activity in rat liver cytosol using the test of radioactive L-citrulline synthesis from L-[guanido-14C]arginine. The three polyamines inhibited inducible NO synthase activity with the following hierarchy: spermine > spermidine approximately equal to putrescine. The 0.5 mM spermine was found to inhibit 50% of inducible NO synthase activity. The present data suggest an inhibitory interrelationship in the liver between two metabolites derived from the common precursor L-arginine.