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Selective MPP+ uptake into synaptic dopamine vesicles: possible involvement in MPTP neurotoxicity
M Del Zompo1, M P Piccardi, S Ruiu
1Department of Neuroscience B. Brodie, University of Cagliari, Italy.
Abstract:
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.
Insights
Researchers found that the toxin 1-methyl-4-phenylpyridinium ion (MPP+) is taken up by synaptic vesicles in mouse striatum, suggesting it shares a carrier with dopamine. This uptake is specific to dopamine-rich brain regions.
Area of Science:
- Neuroscience
- Neuropharmacology
- Molecular Biology
Background:
- The mechanism of dopamine transport into synaptic vesicles is crucial for neurotransmission.
- 1-methyl-4-phenylpyridinium ion (MPP+) is a neurotoxin implicated in Parkinsonism, known to accumulate in dopaminergic neurons.
Purpose of the Study:
- To investigate the mechanism and specificity of MPP+ uptake into synaptic vesicles.
- To determine if MPP+ shares a transport system with dopamine.
Main Methods:
- Studied the saturable, Mg2+/ATP-, and temperature-dependent uptake of MPP+ in synaptic vesicles isolated from mouse striatum.
- Investigated the sensitivity of MPP+ uptake to tetrabenazine, dopamine, and amphetamine.
- Examined the regional distribution of MPP+ uptake in various mouse brain regions.
Main Results:
- MPP+ uptake into striatal synaptic vesicles is saturable and dependent on Mg2+/ATP and temperature.
- MPP+ uptake is inhibited by tetrabenazine, dopamine, and amphetamine, suggesting shared carrier mechanisms with dopamine.
- MPP+ uptake is predominantly found in dopamine-rich regions (striatum, olfactory tubercles, hypothalamus) and absent in dopamine-poor regions (cerebellum, cortex, pons-medulla).
- This region-specific uptake indicates MPP+ as a marker for the dopamine vesicular transporter.
Conclusions:
- Dopamine and MPP+ share a common vesicular transporter in the striatum.
- The differential distribution of MPP+ uptake highlights regional variations in monoamine vesicular carriers.
- MPP+ uptake and vesicular storage may play a role in the neurotoxicity of MPP+ in dopaminergic neurons.