Nitric oxide induces neurotransmitter release from hippocampal slices

Hydroxylamine (1-300 μM), a nitric oxide generator, stimulated the release of [³H]norepinephrine ([³H]NE) and [¹⁴C]acetylchoIine ([¹⁴C]ACh) from rat hippocampal slices in a concentration-dependent manner (EC₅₀ = 30 μM). A maximally effective concentration of hydroxylamine (300 μM) produced a 24-fold increase in the basal [³H]NE and 3.6-fold increase in the in the basal [¹⁴C]ACh efflux. Sodium nitroprusside (SNP), also stimulated the release of [³H]NE, but only at high concentrations (10-30 mM). Calcium-free experimental buffer (1 mM EGTA) abolished the response. Hemoglobin (0.3 μM) inhibited the effect of 100 μM hydroxylamine in a manner which was specific for nitric oxide. In addition, 100 μM hydroxyiarnine increased the efflux of endogenous GABA and glutamate by 3- and 6-fold, respectively.