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  • Title: 1-Methyl-4-phenylpyridinium (MPP+) binds with high affinity to a beta-carboline binding site located on monoamine oxidase type A in rat brain.
    Author: May T.
    Journal: Neurosci Lett; 1993 Nov 12; 162(1-2):55-8. PubMed ID: 8121637.
    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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