Modulation of cerebellar and hepatic nitric oxide synthase by exogenous arginine and endotoxin

Lavinia Cantoni, Federica Di Nicolantonio, Davide Barelli, Milena Rizzardini, Francesco De Matteis

Research output: Contribution to journalArticlepeer-review


We have studied in mice the effect of treatment with exogenous arginine and/or LPS by monitoring serum nitrite/nitrate levels and by investigating the response of cerebellar and liver nitric oxide synthase (NOS). We measured NOS activity in cerebellar extracts while changes in iNOS mRNA were followed in the liver since direct assay of NOS activity proved unreliable with this tissue. In fact, liver and cerebellum extracts were both very active in converting arginine into a citrulline-like metabolite, but only cerebellum conversion was dependent on addition of NADPH and inhibitable by NG-methyl-L-arginine. Treatment with LPS, on its own, increased serum nitrite/nitrate levels at 5 and 20 h after injection, while treatment with LPS and arginine produced nitrite/nitrate levels in the serum even greater at 5 h, but significantly lower at 20 h. Liver iNOS mRNA levels were markedly increased by LPS, and this effect was significantly decreased when mice were also given exogenous arginine. A stimulatory effect of LPS was also found on NOS activity in the cerebellum, where a very small stimulation may have also been caused by arginine feeding. These findings indicate that LPS stimulates NOS expression/activity both in the cerebellum and in the liver and suggest a complex pattern of modulation of iNOS by arginine, with NO being first produced in excess and then downregulating iNOS expression.

Original languageEnglish
Pages (from-to)198-207
Number of pages10
JournalNitric Oxide - Biology and Chemistry
Issue number2
Publication statusPublished - 2001


  • Arginine
  • Cerebellum
  • Endotoxin
  • Inflammation
  • Liver
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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