(3H)GBR-12935 binding sites in human striatal membranes: Binding characteristics and changes in Parkinsonians and schizophrenics.
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概要
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The binding of the Biphenyl-substituted piperazine derivative, [<SUP>3</SUP>H]GBR-12935, a selective dopamine uptake inhibitor, to the post-mortem human putamen was studied. Inhibition curves by dopamine uptake inhibitors suggested the existence of two populations of [<SUP>3</SUP>H]GBR-12935 binding sites: one is potently inhibited by mazindol and/or nomifensine, and the second binding site is benztropine- and/or GBR 12909-sensitive. In the human putamen, [<SUP>3</SUP>H]GBR-12935 labeled both these two distinct binding sites. The [<SUP>3</SUP>H]GBR-12935 binding displaced by mazindol was enriched in the mouse and rat striatum, but not in the cultured mouse neuroblastoma cell N1E-115. The mazindol-sensitive [<SUP>3</SUP>H]GBR-12935 binding site increased in the presence of sodium and markedly decreased in the putamen from parkinsonians (45% of controls). On the other hand, the [<SUP>3</SUP>H]-GBR-12935 binding displaced by benztropine showed no sodium-dependent increase and was not decreased in the putamen from parkinsonians. In the putamen from schizophrenics, the [<SUP>3</SUP>H]GBR-12935 binding did not significantly change in the density, while that displaced by mazindol tended to increase. It is concluded that in the human putamen, [<SUP>3</SUP>H]GBR-12935 binds to two distinct sites. One site is partially sodium-dependent and appears to be associated with a high-affinity dopamine uptake system on dopaminergic nerve terminals. The second binding site shows no sodium-dependency and may be associated with a nondopaminergic and/or extraneuronal DA uptake system.
- 公益社団法人 日本薬理学会の論文
著者
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Nakai Takashi
Department Of Bioscience And Biotechnology Faculty Of Engineering Okayama University
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Hirai Midori
Department Of Applied Biology And Chemistry Faculty Of Applied Bio-science Tokyo University Of Agric
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Kitamura Noboru
Department Of Chemistry Faculty Of Science Hokkaido University
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Mita Tatsuo
Department Of Neuropsychiatry Toyama Medical And Pharmaceutical University
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Shirakawa Osamu
Department Of Neuropsychiatry Kinki University School Of Medicine
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Tanaka Chikako
Department Of Anesthesiology Keio University School Of Medicine
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Yamadori Takashi
Department Of Anatomy 1st Division Kobe Medical College
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Hashimoto Takeshi
Department Of Bioinformatics Graduate School Of Allied Health Sciences Faculty Of Medicine Osaka University
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NOGUCHI-KUNO Sadako
Utano National Hospital
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SHIRAKAWA Osamu
Department of Psychiatry and Neurology, Kobe University School of Medicine
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AMANO Takehiko
Mitsubishi-Kasei Institute of Life Sciences
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KITAMURA Noboru
Department of Pharmacology, Kobe University School of Medicine
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