title: 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.
abstract: 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.
authors.affiliation: Collège de France INSERM U 114, Chaire de Neuropharmacologie, Paris.
authors.forename: T
authors.initials: T
authors.lastname: Galli
authors.forename: G
authors.initials: G
authors.lastname: Godeheu
authors.forename: F
authors.initials: F
authors.lastname: Artaud
authors.forename: J M
authors.initials: JM
authors.lastname: Desce
authors.forename: A
authors.initials: A
authors.lastname: Pittaluga
authors.forename: L
authors.initials: L
authors.lastname: Barbeito
authors.forename: J
authors.initials: J
authors.lastname: Glowsinki
authors.forename: A
authors.initials: A
authors.lastname: Chéramy
mesh_terms: D000818:Animals; D002415:Cats; D003342:Corpus Striatum / Q000378:metabolism* / Q000502:physiology; D003712:Dendrites / Q000378:metabolism* / Q000502:physiology; D004151:Dipeptides / Q000378:metabolism / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D007051:Ibotenic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009411:Nerve Endings / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D013378:Substantia Nigra / Q000378:metabolism* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D004151:Dipeptides; C027172:isospaglumic acid; D007051:Ibotenic Acid; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D004298:Dopamine