SELECTIVE MPP- POSSIBLE INVOLVEMENT IN MPTP NEUROTOXICITY( UPTAKE INTO SYNAPTIC DOPAMINE VESICLES )

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 v esicular uptake suggests that in the striatum dopamine and MPP+ share the vesicular carrier. 3 The presence of MPP+ vesicular uptake in dopa mine-rich regions such as striatum, olfactory, tubercles and hypothala mus, as well as its absence in cerebellum, cortex and pons-medulla, su ggest that monoamine vesicular carriers differ between highly and poor ly dopamine-innervated regions. 4 The restriction of active MPP+ uptak e to the dopaminergic regions, which reflects the previously shown dis tribution of [H-3]-MPP+ binding sites in mouse brain membranes, indica tes MPP+ as a marker of the vesicular carrier for dopamine in dopamine rgic neurones. 5 A role in MPP+ neurotoxicity is suggested for this re gion-specific, vesicular storage of the toxin.