HETEROGENEITY OF MONOAMINERGIC VESICULAR CARRIERS - PHARMACOLOGICAL EVIDENCE USING MPP(+) AS A MARKER

MPP(+) production and uptake by dopaminergic terminals are critical st eps 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 vesi cular carrier. We decided to further characterize such an MPP(+) uptak e. Tetrabenazine inhibits the dopamine uptake both in the striatum and in the cerebellum with similar Km values suggesting an identity of th e vesicular carrier in these areas. On the contrary, H-3-MPP(+) vesicu lar uptake had in the striatum a t1/2 of 60 sec, but was not detectabl e at any time in the cerebellum. Moreover, MPP(+) inhibited the uptake of H-3-DA (Ki: 1.6 +/- 0.03 mu M) and H-3-NE (Ki: 2.6 +/- 0.02 mu M) in the striatum but not in the cerebellum, even at mmolar concentratio n. These pharmacological data indicate that in nondopaminergic areas t he monoamine carrier may be similar but not identical from that locate d in dopaminergic areas.