Characterization of nitric oxide generator-induced hippocampal [3H]norepinephrine release. I. The role of glutamate.
In this study we compared the effects of two nitrogen monoxide (NO) generators, hydroxylamine and S-nitroso-L-cysteine (NO-CYS), on hippocampal [3H]norepinephrine ([3H]NE) release. A 10-min incubation with hydroxylamine (3-3,000 microM) or NO-CYS (30-10,000 microM) induced a concentration-dependent increase in the basal [3H]NE efflux with EC50 values of approximately 100 microM and 1 mM, respectively. Reduced hemoglobin, a NO scavenger, blocked both hydroxylamine- and NO-CYS-evoked [3H]NE release. Long-term exposure (> or = 25 min) to 100 microM hydroxylamine, or to millimolar concentrations of NO-CYS, evoked a tetrodotoxin-insensitive [3H]NE release. However, a 10-min stimulation with either 100 microM hydroxylamine or 300 microM NO-CYS was sensitive to 0.5 microM tetrodotoxin, a voltage-sensitive sodium channel blocker. This suggested that under these conditions hydroxylamine and NO-CYS induce [3H]NE release indirectly in part, perhaps via releasing an excitatory neurotransmitter. Indeed, kynurenate, a nonselective ionotropic glutamate receptor antagonist, produced an 80% inhibition of the NO generator-evoked [3H]NE release. CGS 19755, a N-methyl-D-aspartate receptor antagonist, had no significant effect, whereas the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate receptor antagonists, CNQX and GYKI 52446, inhibited the hydroxylamine response by 50%. In synaptosomes, a preparation in which synaptic interactions are nonsignificant, NO-CYS induced a dose-dependent release of both [3H]NE and [3H]glutamate. These data suggest that, in hippocampal slices, NO generators evoke [3H]NE release both directly from noradrenergic terminals and indirectly via releasing glutamate.
Lonart
G
G
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, USA.
Johnson
K M
KM
D000818:Animals; D002118:Calcium / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000493:pharmacokinetics / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology; D018092:Kainic Acid Receptors / Q000502:physiology; D026403:S-Nitrosothiols; D013268:Stimulation, Chemical; D014316:Tritium; D014665:Vasodilator Agents / Q000494:pharmacology
D002118:Calcium; D006152:Cyclic GMP; D003545:Cysteine; D018698:Glutamic Acid; D019811:Hydroxylamine; D006898:Hydroxylamines; D009569:Nitric Oxide; D009638:Norepinephrine; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D026403:S-Nitrosothiols; D014316:Tritium; D014665:Vasodilator Agents; C021315:S-nitrosocysteine