The nitric oxide donor SNAP-induced amino acid neurotransmitter release in cortical neurons. Effects of blockers of voltage-dependent sodium and calcium channels

• Published in: PloS one 2014-03, Vol.9 (3), p.e90703
• Main Authors: Merino, José Joaquín, Arce, Carmen, Naddaf, Ahmad, Bellver-Landete, Victor, Oset-Gasque, Maria Jesús, González, María Pilar
• Format: Article
• Language: English
• Subjects: Amino acids; Amino Acids - metabolism; Analysis; Animals; Aspartate; Benzoates - pharmacology; Biology; Calcium; Calcium Channel Blockers - pharmacology; Calcium channels; Calcium Channels - metabolism; Cell Survival - drug effects; Cerebral Cortex - cytology; Female; GABA; Glutamate; Glycine; Guanylate Cyclase - antagonists & inhibitors; Guanylate Cyclase - metabolism; High performance liquid chromatography; Imidazoles - pharmacology; Membrane Potentials - drug effects; Models, Biological; Neurons; Neurons - metabolism; Neurotransmitter Agents - metabolism; Nitric oxide; Nitric Oxide Donors - pharmacology; Oxadiazoles - pharmacology; Product introduction; Quinoxalines - pharmacology; Rats; Rats, Wistar; Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors; Receptors, Cytoplasmic and Nuclear - metabolism; S-Nitroso-N-Acetylpenicillamine - pharmacology; Sodium Channel Blockers - pharmacology; Sodium Channels - metabolism; Soluble Guanylyl Cyclase
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0090703

The discovery that nitric oxide (NO) functions as a signalling molecule in the nervous system has radically changed the concept of neuronal communication. NO induces the release of amino acid neurotransmitters but the underlying mechanisms remain to be elucidated. The aim of this work was to study the effect of NO on amino acid neurotransmitter release (Asp, Glu, Gly and GABA) in cortical neurons as well as the mechanism underlying the release of these neurotransmitters. Cortical neurons were stimulated with SNAP, a NO donor, and the release of different amino acid neurotransmitters was measured by HPLC. The involvement of voltage dependent Na+ and Ca2+ channels as well as cGMP in its mechanism of action was evaluated. Our results indicate that NO induces release of aspartate, glutamate, glycine and GABA in cortical neurons and that this release is inhibited by ODQ, an inhibitor of soluble guanylate cyclase. Thus, the NO effect on amino acid neurotransmission could be mediated by cGMP formation in cortical neurons. Our data also demonstrate that the Na+ and Ca2+ voltage- dependent calcium channels are involved in the NO effects on cortical neurons.