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1-Methyl-4-phenylpyridinium (MPP+) binds with high affinity to a beta-carboline binding site located on monoamine
1Institute of Neuropsychopharmacology, Free University, Berlin, FRG.
Abstract:
The in vitro binding of [3H]pargyline and [3H]harman ([3H]1-methyl-beta-carboline) to monoamine oxidase A (MAO-A; EC 1.4.3.4) on membranes of rat cerebral cortex was evaluated. Displacement of the [3H]pargyline binding on MAO-A (L(-)-deprenyl suppressed binding to MAO-B) by harman, 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) revealed IC50 values of 250 +/- 100 nM, 3.1 +/- 0.8 microM, and 5.1 +/- 0.4 microM, respectively. Displacement of the selective, reversible, high-affinity [3H]harman binding to MAO-A revealed inhibition in a competitive manner with Hill coefficients about unity of each compound tested and calculated apparent Ki-values of 4.7 +/- 2.0 nM, 91 +/- 13 nM and 2.4 +/- 0.8 microM, respectively. The data of [3H]harman displacement support the hypothesis of a high-affinity binding site of the neurotoxin MPP+ located on mitochondrial MAO-A with a significant influence on the development of MPTP induced parkinsonism.
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