The biosynthesis of the physiological messenger nitric oxide in neuronal cells is thought to depende on a glial-derived supply of the nitric oxide synthase substrate arginine. toexpand our knowledge of the mechsnism responsible for this glial-neuronal interaction, we studied the possible roles of peroxynitrite anion, superoxide anion, nitric oxide and hydrogen peroxide en L-[H3]-arginine release in cultures astrocytes. after 5 min of incubation at 37 ºC, initialconcentrations of 0.05-2 mM peroxynitrite anion stimulated the release of arginine from astrocytes in a concentratio dependet way; this effect was maximum from 1 mM of peroxynitrite anion and proved tobe 400% as compared with control cells. Peroxynitrite anion mediated arginine release was prevented by arginine transport inhibitors, such as L-lysine and NG-monomethyl-L-arginine, suggesting an involvement of the argine transporter in the effect of peroxynitrite anion.In situ xanthine/xanthine oxidase-generated peroxide anion (20 nmol/min) stimulated arginine release to similar extent to that found with 0.1 mM peroxynitrite anion, but this effect was not prevented by arginine transport inhibitors. Nitric oxide donors, such as sodium nitroprusside, S-nitroso-N- acetylpenicilamine, or 1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium1.-diolate, and hydrogen peroxide did not significantly modify arginine release. As limited arginine availability for neuronal nitric oxide synthase activity may be neurotoxic due to peroxynitrite anion formation, our results suggest that peroxynitrite anion-mediated arginine rekease from astrocytes may contribute to replenishing neuronal arginine, hence avoiding further generation of peroxynitrite anion within these cells.
