1-Methyl-4-phenylpyridinium (MPP+) binds with high affinity to a beta-carboline binding site located on monoamine oxidase type A in rat brain.
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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Institute of Neuropsychopharmacology, Free University, Berlin, FRG.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D002243:Carbolines / Q000378:metabolism* / Q000493:pharmacokinetics; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism; D006247:Harmine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D010293:Pargyline / Q000493:pharmacokinetics; D011726:Pyridinium Compounds / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002243:Carbolines; D011726:Pyridinium Compounds; C048977:1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine; C026560:1-(4-methoxyphenyl)pyridinium; D006247:Harmine; C005010:harman; D010293:Pargyline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase