Cultured astrocytoma cells generate a nitric oxide-like factor from endogenous L-arginine and glyceryl trinitrate: Effect of E. coli lipopolysaccharide

D. Salvemini, V. Mollace, A. Pistelli, E. Anggard, J. Vane

Research output: Contribution to journalArticle

Abstract

1. The inhibitory activity of astrocytoma cells (0.25-3 x 105) treated with indomethacin (10 μM) on platelet aggregation was enhanced by incubating the cells with E. coli lipopolysaccharide (LPS, 0.5 μg ml-1) for 18 h. This effect was attenuated when cycloheximide (10 μg ml-1 was incubated together with LPS. The inhibition of platelet aggregation by cells treated with LPS was potentiated by superoxide dismutase (60 u ml-1) and ablated by oxyhaemoglobin (oxyHb, 10 μM) or N(G)-monomethyl-L-arginine (L-NMMA, 30-300 μM). The effects of L-NMMA were reversed by co-incubation with L-arginine (L-Arg, 100 μM) but not D-arginine (D-Arg, 100 μM). LPS also increased the levels of nitrite in the culture media and this increase was ablated by co-incubation with L-NMMA (300 μM) or cycloheximide (10 μg ml-1). 2. Astrocytoma cells (0.5 x 105) treated with indomethacin (10 μM) enhanced the platelet inhibitory activity of glyceryl trinitrate (GTN, 11-352 μM) but not that of sodium nitroprusside (4 μM). Furthermore, when incubated with GTN (200 μM) a 4 fold increase in the levels of guanosine 3':5-cyclic monophosphate (cyclic GMP) was observed. These effects were abrogated by co-incubation with oxyHb (10 μM) but not with L-NMMA (300 μM). Treatment of the cells with LPS (0.5 μg ml-1) for 18 h did not enhance their capacity to form NO from GTN. 3. Thus, in cultured astrocytoma cells, LPS enhances the formation of nitric oxide from endogenous L-arginine. In addition, these cells can metabolize GTN to nitric oxide but this process is not enhanced by LPS stimulation.

Original languageEnglish
Pages (from-to)931-936
Number of pages6
JournalBritish Journal of Pharmacology
Volume106
Issue number4
Publication statusPublished - 1992

Keywords

  • Astrocytoma cells
  • E. coli lipopolysaccharide
  • Glyceryl trinitrate
  • Nitric oxide

ASJC Scopus subject areas

  • Pharmacology

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