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 (OONO-), modulates the release of neurotransmitters from neuronal tissues. Although we reported that S-nitroso-cysteine stimulated noradrenaline release in brain slices, we now show that only S-nitroso-cysteine inhibits noradrenaline release from PC12 cells. S-Nitroso-cysteine inhibited, in a dose-dependent manner (up to 0.6 mM), the Ca2+ -dependent [3H]noradrenaline release induced by ionomycin, adenosine 5'-O-(3-thiotriphosphate), or high K+, from PC12 cells labeled with [3H]noradrenaline. Sodium nitroprusside, S-nitroso-N-acetylpenicillamine, and 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene, which specifically release NO free radicals in neutral buffer, had minimal effects on [3H]noradrenaline release, although they markedly stimulated cyclic GMP accumulation. 3-Morpholinosydonimine, which releases peroxynitrite, had no effect on either [3H]noradrenaline release or cyclic GMP accumulation. S-Nitroso-cysteine inhibited phorbol 12-myristate 13-acetate- and mastoparan (wasp venom toxin)-induced [3H]noradrenaline release. These findings 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 inhibitory effects of S-nitroso-cysteine in PC12 cells.