Regulation of noradrenaline release by S-nitroso-cysteine: inhibition in PC12 cells in a cyclic GMP independent manner

Nitric oxide (NO), including NO free radicals (. NO) and peroxynitrite (OON O-), modulates the release of neurotransmitters from neuronal tissues. Alth ough we reported that S-nitroso-cysteine stimulated noradrenaline release i n brain slices, we now show that only S-nitroso-cysteine inhibits noradrena line release from PC12 cells. S-Nitroso-cysteine inhibited, in a dose-depen dent manner (up to 0.6 mM), the Ca2+-dependent [H-3]noradrenaline release i nduced by ionomycin, adenosine 5'-O-(3-thiotriphosphate), or high K+, from PC12 cells labeled with [H-3]noradrenaline. Sodium nitroprusside, S-nitroso -N-acetylpenicillamine, and 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazen e, which specifically release NO free radicals in neutral buffer, had minim al effects on [H-3]noradrenaline release, although they markedly stimulated cyclic GMP accumulation. 3-Morpholinosydonimine, which releases peroxynitr ite, had no effect on either [H-3]noradrenaline release or cyclic GMP accum ulation. S-Nitroso-cysteine inhibited phorbol 12-myristate 13-acetate- and mastoparan (wasp venom toxin)-induced [H-3]noradrenaline release. These fin dings suggest that 1) S-nitroso-cysteine, but not other NO donors, inhibits some common process occurring during noradrenaline release in PC12 cells, 2) neither NO radicals, peroxynitrite, nor cyclic GMP mediate the inhibitor y effects of S-nitroso-cysteine in PC12 cells. (C) 1998 Elsevier Science B. V. All rights reserved.