SODIUM-NITROPRUSSIDE STIMULATES NORADRENALINE RELEASE FROM RAT HIPPOCAMPAL SLICES IN THE PRESENCE OF DITHIOTHREITOL

It is becoming apparent that nitrogen monoxide (NO) such as nitric oxi de has regulatory roles for neuronal cell functions. We examined the r ole of NO using NO donors on [H-3]noradrenaline (NA) release from prel abeled rat hippocampal slices. Sodium nitroprusside (SNP), which had n o effect by itself, stimulated [H-3]NA release in a dose-dependent man ner (ED(50) = 0.5 mM) in the presence of dithiothreitol (DTT). The sti mulatory effect of SNP with DTT, but not high-K+, was observed in an e xtracellular Ca2+-free buffer. The maximal effect of SNP was obtained after incubation for 1-2 h with DTT in buffer at physiological pH (7.4 ). The simultaneous addition of SNP and DTT to the slices induced a sm all effect, and the effect of SNP-declined after 3.5 h. SNP stimulated cyclic GMP accumulation in the slices without DTT. NaNO2 and 1-hydrox y-2-oxo-3,3-bis(2-aminoethyl)-1-triazene (a generator of nitric oxide) , which stimulated cyclic GMP accumulation by themselves, did not stim ulate [H-3]NA release in the presence and absence of DTT. 3-Morpholino sydnonimine HCl (a generator of peroxynitrite) had no effect on the re lease. The stimulatory effect of SNP and DTT on NA release was inhibit ed 40% by nitric oxide scavengers such as oxyhemoglobin and nyl)-4,4,5 ,5-tetramethylimidazoline-1-oxy-3-oxide, although cyclic GMP accumulat ion induced by NO donors was completely inhibited. These findings sugg est that SNP reacts with DTT to produce unknown active species, and th at cyclic GMP is not a mediator for SNP-stimulated NA release.