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Heterogeneity of monoaminergic vesicular carriers: pharmacological evidence using MPP+ as a marker
S Ruiu1, M P Piccardi, A Bocchetta
1Department of Neurosciences B.B. Brodie, University of Cagliari, Italy.
Abstract:
MPP-production and uptake by dopaminergic terminals are critical steps in MPTP-induced Parkinson-like disorder. We reported evidence for a specific uptake of MPP by synaptic vesicles from mouse striatum. Its regional distribution suggests it as a marker of the dopamine vesicular carrier. We decided to further characterize such an MPP uptake. Tetrabenazine inhibits the dopamine uptake both in the striatum and in the cerebellum with similar Km values suggesting an identify of the vesicular carrier in these areas. On the contrary, 3H-MPP vesicular uptake had in the striatum a t1/2 of 60 sec, but was not detectable at any time in the cerebellum. Moreover, MPP inhibited the uptake of 3H-DA (Ki: 1.6 +/- 0.03 microM) and 3H-NE (Ki 2.6 +/- 0.01 microM) in the striatum but not in the cerebellum, even at molar concentration. These pharmacological data indicate that in nondopaminergic areas the monoamine carrier may be similar but not identical from that located in dopaminergic areas.
Insights
MPP uptake by synaptic vesicles is crucial in Parkinsonism. This study shows MPP vesicular uptake differs between dopaminergic and nondopaminergic brain areas, suggesting distinct monoamine carriers.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- MPP production and uptake are key in MPTP-induced Parkinson-like disorders.
- Previous work suggested MPP uptake by synaptic vesicles in the mouse striatum as a marker for the dopamine vesicular carrier.
Purpose of the Study:
- To further characterize the specific uptake of MPP by synaptic vesicles.
- To investigate the pharmacological properties of the vesicular carrier in different brain regions.
Main Methods:
- Investigated MPP vesicular uptake in mouse striatum and cerebellum.
- Utilized tetrabenazine to assess dopamine uptake inhibition.
- Measured inhibition of 3H-DA and 3H-NE uptake by MPP.
Main Results:
- Tetrabenazine inhibited dopamine uptake similarly in striatum and cerebellum.
- 3H-MPP vesicular uptake was rapid in the striatum but undetectable in the cerebellum.
- MPP inhibited dopamine and norepinephrine uptake in the striatum but not the cerebellum.
Conclusions:
- Pharmacological data suggest that monoamine carriers in nondopaminergic areas are similar but not identical to those in dopaminergic areas.
- MPP vesicular uptake serves as a marker differentiating dopaminergic and nondopaminergic monoamine carriers.