Specific role of N-acetyl-aspartyl-glutamate in the in vivo regulation of dopamine release from dendrites and nerve terminals of nigrostriatal dopaminergic neurons in the cat.

Article date: 1991/1/1

PubMed ID: 1861773

Journal name: Neuroscience (ISSN: 0306-4522)


Levels of N-acetyl-aspartyl-glutamate measured by high-pressure liquid chromatography were found to be very high in the cat substantia nigra, particularly in the pars compacta, while those in the caudate nucleus were much lower. In halothane-anaesthetized cats implanted with push-pull cannulae, N-acetyl-aspartyl-glutamate (10(-8) M) induced a marked and prolonged release of newly synthesized [3H]dopamine, when infused into the posterior but not into the anterior part of the caudate nucleus. In contrast, in the presence of tetrodotoxin (10(-6) M), N-acetyl-aspartyl-glutamate (10(-8) M) reduced the residual release of [3H]dopamine; this effect was also more pronounced in the posterior than in the anterior part. In the conditions used, as indicated by experiments with [3H]N-acetyl-aspartyl-glutamate no glutamate was formed from the infused N-acetyl-aspartyl-glutamate. Ibotenate (10(-5) M) induced changes in [3H]dopamine release in both the absence and presence of tetrodotoxin, which were closely similar to those observed with N-acetyl-aspartyl-glutamate. Responses induced by either N-acetyl-aspartyl-glutamate or ibotenate were not mediated by N-methyl-D-aspartate receptors since N-methyl-D-aspartate stimulated the release of [3H]dopamine only when used in a high concentration (10(-4) M) and applied in a magnesium-free superfusion medium in both the presence of glycine (10(-6) M) and strychnine (10(-6) M). In addition, the stimulatory effect of N-methyl-D-aspartate persisted in the presence of tetrodotoxin; it was of similar amplitude in both parts of the caudate nucleus and of shorter duration than that evoked by either N-acetyl-aspartyl-glutamate or ibotenate alone. N-Acetyl-aspartyl-glutamate interacted with dopaminergic neurons not only presynaptically in the caudate nucleus but also in the substantia nigra since a marked increase in [3H]dopamine release was observed both from local dendrites and from nerve terminals in the ipsilateral caudate nucleus when N-acetyl-aspartyl-glutamate (10(-7) M) was infused locally into the substantia nigra pars compacta. No effect could be seen in contralateral structures. The isomer of natural N-acetyl-aspartyl-glutamate, beta-N-acetyl-aspartyl-glutamate (10(-7) M), had no effect on [3H]dopamine release when applied similarly in the substantia nigra, thus confirming the specificity of the action of N-acetyl-aspartyl-glutamate.

Author List: Galli T, Godeheu G, Artaud F, Desce J M, Pittaluga A, Barbeito L, Glowsinki J, Chéramy A

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Dipeptides; isospaglumic acid; Ibotenic Acid; Tetrodotoxin; N-Methylaspartate; Dopamine;

Mesh terms: Animals; Cats; Corpus Striatum/metabolism; Dendrites/metabolism; Dipeptides/metabolism; Dopamine/metabolism; Female; Ibotenic Acid/pharmacology; Male; N-Methylaspartate/pharmacology; Nerve Endings/metabolism; Neurons/metabolism; Substantia Nigra/metabolism; Tetrodotoxin/pharmacology;

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