Effect of the tetraphenylboron ion on the inhibition of mitochondrial respiration in synaptosomes by the 1-methyl-4-phenylpyridinium ion (MPP(+)).
The effects of the 1-methyl-4-phenylpyridinium ion (MPP(+)) and some structurally related compounds on mitochondrial respiration and lactate production in mouse brain synaptosomes were studied with and without tetraphenylboron (TPB(?)), an activator of membrane transport of lipophilic cations. Without TPB(?), both MPP(+) and 4-phenylpyridine (4-PP), at concentrations of 1 mM, weakly inhibited synaptosomal respiration, but paraquat and 4-phenyl-1,2,3,6-tetrahydropyridine (PTP) did not. In the presence of 10 ?M TPB(?), MPP(+), at lower concentrations, significantly inhibited respiration and increased lactate production, but these two effects with 4-PP were not as great as those with MPP(+). Regardless of TPB(?), paraquat did not affect respiration or lactate production, but PTP, with TPB(?), somewhat accelerated both systems. In these experiments, except PTP, the degree of increase in lactate production caused was in close parallel with that of the inhibition of synaptosomal respiration. The present results conclusively indicate that, without TPB(?), MPP(+) scarcely permeates synaptosomal membranes of mouse whole brain. The present results confirm previous findings that nigrostriatal dopamine neurons, which selectively take up MPP(+) by the DA transport system, may be more selectively damaged by concentrated MPP(+) than other neurons that essentially lack a transport system with poor permeability for MPP(+) through their neuronal membranes.
Aiuchi
T
T
Laboratory of Biological Chemistry, School of Pharmaceutical Sciences, Hatanodai, Shinagawa-ku, Tokyo 142, Japan.
Shirane
Y
Y
Kinemuchi
H
H
Arai
Y
Y
Kim
S K
SK
Nakaya
K
K
Nakamura
Y
Y