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 oxide has regulatory roles for neuronal cell functions. We examined the role of NO using NO donors on [3H]noradrenaline (NA) release from prelabeled rat hippocampal slices. Sodium nitroprusside (SNP), which had no effect by itself, stimulated [3H]NA release in a dose-dependent manner (ED50 = 0.5 mM) in the presence of dithiothreitol (DTT). The stimulatory effect of SNP with DTT, but not high K+, was observed in an extracellular Ca(2+)-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 small effect, and the effect of SNP declined after 3.5 h. SNP stimulated cyclic GMP accumulation in the slices without DTT. NaNO2 and 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene (a generator of nitric oxide), which stimulated cyclic GMP accumulation by themselves, did not stimulate [3H]NA release in the presence and absence of DTT. 3-Morpholinosydnonimine HC1 (a generator of peroxynitrite) had no effect on the release. The stimulatory effect of SNP and DTT on NA release was inhibited 40% by nitric oxide scavengers such as oxyhemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide, although cyclic GMP accumulation induced by NO donors was completely inhibited. These findings suggest that SNP reacts with DTT to produce unknown active species, and that cyclic GMP is not a mediator for SNP-stimulated NA release.
Satoh
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Murayama
T
T
Nomura
Y
Y
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology*; D004347:Drug Interactions; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010108:Oxyhemoglobins / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012977:Sodium Nitrite / Q000494:pharmacology
D001565:Benzoates; D007093:Imidazoles; C093285:NOC 18; D009603:Nitroso Compounds; D010108:Oxyhemoglobins; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009599:Nitroprusside; D009569:Nitric Oxide; D011189:Potassium Chloride; D006152:Cyclic GMP; D012977:Sodium Nitrite; D002118:Calcium; D004229:Dithiothreitol; D009638:Norepinephrine