Uptake of 1-Methyl-4-phenylpyridinium Ion (MPP^+) and ATP Content in Synaptosomes

概要

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Symptoms such as those in Parkinson's disease are known to be induced by the neurotoxin, 1-methyl-4-phenylpyridinium (MPP^+). We tried to quantitatively measure synaptosomal MPP^+ uptake using an MPP^+ selective electrode to study the correlation between MPP^+ uptake and respiratory inhibition. Synaptosomal MPP^+ uptake was low but could be increased by the addition of glucose as an energy substrate, or increased with an increase in the concentration of MPP^+. The rate of uptake was 0.2 nmol/mg protein/min at 50μM MPP^+. Tetraphenylboron (TPB^-), which enhances cation permeability, increased MPP^+ uptake, and the increase was proportional to the TPB^- concention. When external MPP^+ concentration was increased above 200μM, ATP was depleted and the uptake of MPP^+ decreased, which resulted in the release of intrasynaptosomal MPP^+. MPP^+ uptake was also decreased by depolarization of the membrane potential in synaptosomes. MPP^+ was presumed to be distributed across both the synaptosomal and inner mitochondrial membranes, and to be affected by membrane potential as a lipophilic cation. When respiration of the inner mitochondria was inhibited by increasing the intrasynaptosomal MPP^+ concentration, the concentration of MPP^+ in cytosol was presumed to increase by the release of MPP^+ from the mitochondria, and synaptosomal MPP^+ uptake would then be decreased.
公益社団法人日本薬学会の論文
1996-01-15