title: Autoreceptor presynaptic control of dopamine release from striatum is lost at early stages of manganese poisoning.
abstract: Manganese (Mn) poisoning in man produces an early psychotic disorder that is later followed by a Parkinson-like syndrome. Since alterations in the brain DA system are thought to be involved, we assessed the presynaptic autoreceptor regulation of K(+)-evoked 3H-DA release from superfused striatal slices of mice treated i.p. with 5 mg Mn/kg weight/day for 2 and 8 weeks. Mn poisoning did not change basal and evoked DA release. In controls, 1 microM apomorphine (APO), a D2-like DA receptor agonist, produced an inhibition of K(+)-evoked 3H-DA release that was blocked by the D2-like DA receptor antagonist, S(-)-sulpiride (1 microM). Yet, APO lost its capacity to inhibit the K(+)-evoked 3H-DA release after 2 weeks of Mn poisoning. After 8 weeks of Mn poisoning, APO was again able to reduce K(+)-evoked 3H-DA release. MK-801 (0.3 microM), a NMDA-glutamate receptor antagonist, could restore APO inhibitory control on DA release lost at week 2 of Mn poisoning. These findings suggest a NMDA-glutamate-receptor-mediated loss of autoreceptor presynaptic control of striatal DA release at early Mn poisoning.
authors.affiliation: Section of Neurochemistry, School of Medicine, Universidad del Zulia, Maracaibo, Venezuela.
authors.forename: M C
authors.initials: MC
authors.lastname: Cuesta de Di Zio
authors.forename: G
authors.initials: G
authors.lastname: Gómez
authors.forename: E
authors.initials: E
authors.lastname: Bonilla
authors.forename: H
authors.initials: H
authors.lastname: Suarez-Roca
mesh_terms: D000818:Animals; D017660:Autoreceptors / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D008345:Manganese / Q000378:metabolism; D020149:Manganese Poisoning; D051379:Mice; D017729:Presynaptic Terminals / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D017660:Autoreceptors; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D008345:Manganese; D004298:Dopamine