Uptake of 1-methyl-4-phenylpyridinium ion (MPP+) and ATP content in synaptosomes.
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 50 microM MPP+. Tetraphenylboron (TPB+), which enhances cation permeability, increased MPP+ uptake, and the increase was proportional to the TPB+ concentration. When external MPP+ concentration was increased above 200 microM, 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.
Matsunaga
M
M
School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Shirane
Y
Y
Aiuchi
T
T
Nakamura
Y
Y
Nakaya
K
K
D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D015259:Dopamine Agents / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013775:Tetraphenylborate / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology; D014702:Veratrine / Q000494:pharmacology
D015259:Dopamine Agents; D014475:Uncoupling Agents; D013775:Tetraphenylborate; D000255:Adenosine Triphosphate; D014702:Veratrine; D015655:1-Methyl-4-phenylpyridinium; D011188:Potassium