Selective MPP+ uptake into synaptic dopamine vesicles: possible involvement in MPTP neurotoxicity.
1. In the present study we provide evidence for a saturable, Mg2+/ATP- and temperature-dependent, tetrabenazine-, dopamine-, and amphetamine-sensitive uptake of 1-methyl-4-phenylpyridinium ion (MPP+) in synaptic vesicles from mouse striatum. 2. Similarity in the properties of the vesicular uptake suggests that in the striatum dopamine and MPP+ share the vesicular carrier. 3. The presence of MPP+ vesicular uptake in dopamine-rich regions such as striatum, olfactory, tubercles and hypothalamus, as well as its absence in cerebellum, cortex and pons-medulla, suggest that monoamine vesicular carriers differ between highly and poorly dopamine-innervated regions. 4. The restriction of active MPP+ uptake to the dopaminergic regions, which reflects the previously shown distribution of [3H]-MPP+ binding sites in mouse brain membranes, indicates MPP+ as a marker of the vesicular carrier for dopamine in dopaminergic neurones. 5. A role in MPP+ neurotoxicity is suggested for this region-specific, vesicular storage of the toxin.
Del Zompo
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M
Department of Neuroscience B. Brodie, University of Cagliari, Italy.
Piccardi
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Ruiu
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Quartu
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Gessa
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Vaccari
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D015259:Dopamine Agents / Q000633:toxicity*; D066298:In Vitro Techniques; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism; D011726:Pyridinium Compounds / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism*; D013747:Tetrabenazine / Q000494:pharmacology
D015415:Biomarkers; D015259:Dopamine Agents; D011726:Pyridinium Compounds; C048977:1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine; C026560:1-(4-methoxyphenyl)pyridinium; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000661:Amphetamine; D004298:Dopamine; D013747:Tetrabenazine