Heterogeneity of monoaminergic vesicular carriers: pharmacological evidence using MPP+ as a marker

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 identity of the vesicular carrier in these areas. On the contrary, 3H-MPP+ vesicular uptake had in the striatum a t 1/4 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 μM) and 3H-NE (Ki: 2.6 ± 0.01 μM) in the striatum but not in the cerebellum, even at mmolar concentration. These pharmacological data indicate that in nondopaminergic areas the monoamine carrier may be similar but not identical from that located in dopaminergic areas.