Dissociated release of tetrahydrobiopterin and nitric oxide by lipopolysaccharide from mouse neuroblastoma cells.

We examined the release of tetrahydrobiopterin ((6R)-L-erythro-dihydroxypropyl-2-amino-4-hydroxy-5,6,7, 8-tetrahydropteridine; BH4) and nitric oxide induced by lipopolysaccharide from mouse neuroblastoma N1E-115 cells by measuring BH4 and nitric oxide derivatives, nitrites and nitrates, harbored in the conditioned media. The stimulation of the cells by 1 microgram/ml of lipopolysaccharide for 24 h induced 2-fold increase in the release of BH4 from the cells, but did not induce the nitric oxide release from the cells. Although such increase in BH4 release from the cells was blocked by the inhibitors of nuclear factor-kappa B or protein tyrosine kinases, the release of nitric oxide was not affected by such inhibitors. Our results may suggest that the inductions of BH4 and nitric oxide in this neuroblastoma cell line are processed in different ways and that this cell line is also different from the immune cells in the central nervous system such as microglia in this respect.