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

Abstract

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 Ca 2+-dependent [ 3 H] noradrenaline release induced by ionomycin, adenosine 5′- O-(3-thiotriphosphate), or high K +, from PC12 cells labeled with [ 3 H] 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 [ 3 H] noradrenaline release, although they markedly stimulated cyclic GMP accumulation. 3-Morpholinosydonimine, which releases peroxynitrite, had no effect on either [ 3 H] noradrenaline release or cyclic GMP accumulation. S-Nitroso-cysteine inhibited phorbol 12-myristate 13-acetate- and mastoparan (wasp venom toxin)-induced [ 3 H] 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.