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Participation of brain monoamine oxidase B form in the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: Relationship between the enzyme inhibition and the neurotoxicity

Authors
Journal
Neuroscience Letters
0304-3940
Publisher
Elsevier
Publication Date
Volume
58
Issue
2
Identifiers
DOI: 10.1016/0304-3940(85)90163-6
Keywords
  • 1-Methyl-4-Phenyl-1
  • 2
  • 3
  • 6-Tetrahydropyridine
  • Mptp
  • 1-Methyl-4-Phenylpyridinium
  • Mpp+
  • Neurotoxicity
  • Monoamine Oxidase
  • Monoamine Oxidase A
  • Monoamine Oxidase B
  • Suicide Inhibition
  • Parkinson'S Disease

Abstract

Abstract A neurotoxin for nigrostriatal dopaminergic neurons, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its oxidized metabolite, 1-methyl-4-phenylpyridine (MPP +), both dose-dependently inhibited rat striatal and forebrain monoamine oxidase (MAO) activity with monoamine oxidase A (MAO-A) selectively reversible (competitive, K i = 4.5 and 2.0 μM) inhibition. A comparison of the K i values indicated the affinity of MPP + for MAO-A to be greater than that of MPTP. MPTP inhibited monoamine oxidase B (MAO-B) with both a reversible (competitive, K i = 116 μM) and an irreversible time-dependent component, but inhibition by MPP + was reversible and competitive ( K i = 180 μM). These results, together with previous findings on metabolism of MPTP to MPP + by brain MAO-B, suggest that MPP + is a simple inhibitor of MAO-A and MAO-B, but MPTP might be a ‘suicide substrate’ inhibitor for MAO-B.

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