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Mechanism of Accumulation of the 1‐methyl‐4‐Phenylpyridinium Species into Mouse Brain Synaptosomes
Author(s) -
Scotcher Kevin P.,
Irwin Ian,
DeLanney Louis E.,
Langston J. William,
Monte Donate
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb02057.x
Subject(s) - nomifensine , chemistry , depolarization , biophysics , synaptosome , membrane potential , hyperpolarization (physics) , mazindol , metabolite , mptp , membrane , mitochondrion , incubation , catecholamine , neurotoxin , biochemistry , dopamine , endocrinology , stereochemistry , biology , dopaminergic , nuclear magnetic resonance spectroscopy
The mechanism of accumulation of 1‐methyl‐4‐phenylpyridinium ion (MPP + ), the toxic metabolite of 1‐methyl‐4‐phenyl‐l,2,3,6‐tetrahydropyridine, into neuronal terminals was studied using mouse brain synaptosomes as an in vitro model. Addition of MPP + to synaptosomal preparations, essentially devoid of contamination by extrasynap‐tosomal mitochondria, resulted in its time‐ and concentration‐dependent accumulation. Intrasynaptosomal concentrations of 79 and 106 μ M were reached 10 and 30 min, respectively, after addition of 50 μ M MPP + . The accumulation of 50 μ M MPP + into synaptosomes was only slightly affected by the catecholamine uptake blockers mazindol and nomifensine; in contrast, it was markedly enhanced by tetra‐phenylborate, a lipophilic anion that increases the rate of accumulation of permeant cations via a Nernstian concentration gradient. MPP + accumulation was significantly increased or decreased as a consequence of hyperpolarization or depolarization, respectively, of the plasma membrane of synaptosomes. This effect was evident after incubation for 10 min. Changes in mitochondrial membrane potential also affected MPP + accumulation, although only after 30 min of incubation. Data indicate that polarization of neuronal membranes may significantly contribute to the accumulation of MPP + into nerve terminals.