Presynaptic N-methyl-D-aspartate receptor activation inhibits neurotransmitter release through nitric oxide formation in rat hippocampal nerve terminals

Brain Research. Molecular Brain Research
S M SequeiraC M Carvalho

Abstract

In brain synapses, nitric oxide synthase activation is coupled to N-methyl-D-aspartate-mediated calcium entry at postsynaptic densities through regulatory protein complexes, however a presynaptic equivalent to this signaling mechanism has not yet been identified. Novel evidence indicates that N-methyl-D-aspartate glutamate receptors may play a presynaptic role in synaptic plasticity. Thus, we investigated whether ionotropic glutamate receptor activation in isolated nerve terminals regulates neurotransmitter release, through nitric oxide formation. N-Methyl-D-aspartate dose-dependently inhibited the release of glutamate evoked by 4-aminopyridine (IC(50)=155 microM), and this effect was reversed by the N-methyl-D-aspartate receptor antagonist D-(-)-2-amino-5-phosphopentanoic acid and by the nitric oxide synthase inhibitor, L-nitroarginine, in synaptosomes isolated from whole hippocampus, CA3 and CA1 areas, but not from the dentate gyrus. In contrast, the 4-aminopyridine-evoked release of glutamate was reduced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or kainate by a nitric oxide-independent mechanism, since it was not blocked by L-nitroarginine, and N-methyl-D-aspartate, but not alpha-amino-3-hydroxy-5-methyl-4-...Continue Reading

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Citations

Mar 3, 2005·Journal of Neurology·Marie DagonnierMario Manto
May 14, 2003·Neurochemistry International·Pirjo Saransaari, Simo S Oja
Sep 9, 2006·Clinical Neuropharmacology·Giuseppe MecoLetterio Morgante
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Apr 15, 2014·European Journal of Pharmacology·Che-Chuan WangSu-Jane Wang
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Jul 5, 2008·Neurochemical Research·Pirjo Saransaari, Simo S Oja
Apr 8, 2017·Journal of Immunology Research·Hiroshi MitomaChristiane S Hampe
Oct 18, 2007·Neurochemical Research·Pirjo Saransaari, Simo S Oja
Aug 4, 2005·Neurochemical Research·Rejane G TavaresDiogo O Souza
Aug 23, 2007·Neurochemical Research·Pirjo Saransaari, Simo S Oja

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