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

Abstract

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.

Biology of Parkinson's disease: pathogenesis and pathophysiology of a multisystem neurodegenerative disorder

“…The search for environmental factors that might initiate or enhance the neurodegenerative process in PD intensified following the discovery of MPTP-induced parkinsonism. As oxidative stress had been clearly implicated in the pathogenesis of MPTP-induced parkinsonism, 14 , 133 it was natural to focus to some extent, on environmental oxidants and inhibitors of mitochondrial respiration. Tetrahydroisoquinoline (TIQ) and β-carboline (β-C) derivatives, which are structurally related to MPTP and occur naturally in many foods, produce nigrostriatal damage in experimental animals and have been detected in brain and cerebrospinal fluid (CSF) in PD patients.…”

1‐Methyl‐4‐phenylpridinium (MPP+)‐induced functional run‐down of GABAA receptor‐mediated currents in acutely dissociated dopaminergic neurons

“…Scotcher et al (1990) measured intracellular ATP concentation in a mouse brain synaptosomes preparation after incubation in MPTP or MPP + , and found that a significant reduction of intracellular ATP level occurred after a 15-min, incubation in 0.05 or 0.1 mM MPP + . Using an MPP + selective electrode, Matsunaga et al (1996) found that in the presence of 10 mM glucose, synaptosomal MPP + uptake was very fast, reaching 75% within 3 min, 85% in 6 min, and maximal uptake occurring in 9 min. Moseley et al (1997) measured 1 mM [ 3 H]MPP + uptake in rat liver plasma membrane vesicles, and found that MPP + uptake was significantly increased within 1 min.…”