title: Differential effects of nitric oxide gas and nitric oxide donors on depolarization-induced release of [3H]norepinephrine from rat hippocampal slices.
abstract: The NO-generating compounds sodium nitroprusside (NP), nitroglycerin (NTG), and isosorbide dinitrate (ISDN) all significantly inhibited N-methyl-D-aspartate (NMDA)-stimulated release of tritiated norepinephrine ([3H]NA) from preloaded hippocampal slices of adult male Sprague-Dawley rats with IC50's of 114 microM, 1.2 mM, and 1.7 mM respectively. NTG and ISDN also inhibited KCl-stimulated release, while NP had no significant effect on KCl-stimulated release. Although these results suggest that the inhibitory effects of these compounds were mediated by release of NO, NTG and ISDN did not generate detectable levels of NO, and iron-cyanide complexes similar in structure to NP but lacking NO also inhibited release. In contrast, both S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and authentic NO gas significantly enhanced NMDA-stimulated release of [3H]NA (EC50's: 331 and 3.4 microM respectively). This enhancement was not selective for NMDA-stimulated release, since both SNAP and NO potentiated KCl-stimulated release as well. In addition, NO gas significantly enhanced NMDA-stimulated release of tritiated dopamine ([3H]DA) from striatal slices and [3H]NA from cortical and cerebellar slices. Analogs of cyclic guanosine monophosphate (cGMP) had no significant effect on NMDA-stimulated transmitter release, suggesting that the observed increase in release is via a cGMP-independent mechanism. While exogenous NO enhanced both NMDA- and KCl-stimulated neurotransmitter release, it appears that endogenous NO does not play a role in this depolarization-induced release since NO synthase inhibitors did not significantly reduce NMDA-stimulated [3H]NA release. The possibility remains that endogenous NO could modulate neurotransmitter release in other circumstances.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
authors.forename: A K
authors.initials: AK
authors.lastname: Stout
authors.forename: J J
authors.initials: JJ
authors.lastname: Woodward
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D005295:Ferrocyanides / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019001:Nitric Oxide Synthase; D009638:Norepinephrine / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005295:Ferrocyanides; D009467:Neuromuscular Depolarizing Agents; D009569:Nitric Oxide; D016202:N-Methylaspartate; D011189:Potassium Chloride; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C020354:hexacyanoferrate II; D006152:Cyclic GMP; D004298:Dopamine; D009638:Norepinephrine