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Analysis of the effects of MPTP on the monoamine metabolic system—Effects on tyrosine hydroxylase (TH) activity. Toshiharu NAGATSU 1 1Department of Biochemistry, Nagoya University School of Medicine pp.838-850
Published Date 1987/10/10
DOI https://doi.org/10.11477/mf.1431905934
  • Abstract
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Tyrosine hydroxylase (TH) activity in vitro (Vmax) was reduced in the striatum and substantia nigra from the patients with Parkinson's disease to approximately 10% of that from the control patients. TH reduction only in the striatum, but not in the substantia nigra, was found in a case of juvenile Parkinson's disease. The acute administration of MPTP (30 mg/kg, s.c., 1 h prior to sacrifice) in mice resulted in a decrease of tyrosine hydroxylation in situ in tissue slices but not in vitro in homogenates. In contrast, repeated injection of MPTP (30 mg/kg s.c. daily for 8 days) caused a decrease of TH activity both in vitro in homogenate and in situ in tissue slices, and the decrease of TH protein in the striatum was also confirmed by enzyme immunoassay of TH protein and by immunohistochemistry of TH. The late reduction in TH activity and protein by repeated treatment of mice with MPTP may be caused by the loss of the nerve terminals of the nigrostriatal dopaminergic neu-rons. The acute inhibition of the TH system in situ in tissue slices by MPTP was found to be prevented by a monoamine oxidase inhibitor and by a dopamine uptake inhibitor, but that by MPP+ was not prevented by a monoamine oxidase inhibitor and was prevented only by a dopamine uptake inhibitor. The inhibition of the TH system by MPP+ analogues was applied for the screening of nigrostriatal dopaminergic neurotoxins. As a result, tetrahydroisoquinoline-related compounds were thought to be such neurotoxin candidates. Tetrahydroisoquinoline had a slight but significant effect on the reduction TH in the striatum of mice after repeated injection. Tetrahydroisoquinoline and 2-methyl-tetrahydroquinoline were identified in the human brain for the first time from parkinsonian patients and normal controls. The concentration of 2-methyl-tetrahydroquinoline was similar between parkinsonian and control brains, whereas the concentration of tetrahydroisoquinoline was markedly higher in the parkinsonian brain than in the normal brain.


Copyright © 1987, Igaku-Shoin Ltd. All rights reserved.

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電子版ISSN 1882-1243 印刷版ISSN 0001-8724 医学書院

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