title: [3H]GBR-12935 binding sites in human striatal membranes: binding characteristics and changes in parkinsonians and schizophrenics.
abstract: The binding of the diphenyl-substituted piperazine derivative, [3H]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 [3H]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, [3H]GBR-12935 labeled both these two distinct binding sites. The [3H]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 [3H]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 [3H]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 [3H]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, [3H]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.
authors.affiliation: Department of Pharmacology, Kobe University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hirai
authors.forename: N
authors.initials: N
authors.lastname: Kitamura
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Nakai
authors.forename: T
authors.initials: T
authors.lastname: Mita
authors.forename: O
authors.initials: O
authors.lastname: Shirakawa
authors.forename: T
authors.initials: T
authors.lastname: Yamadori
authors.forename: T
authors.initials: T
authors.lastname: Amano
authors.forename: S A
authors.initials: SA
authors.lastname: Noguchi-Kuno
authors.forename: C
authors.initials: C
authors.lastname: Tanaka
mesh_terms: D000368:Aged; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism*; D010879:Piperazines / Q000378:metabolism*; D011699:Putamen / Q000378:metabolism; D051381:Rats; D012559:Schizophrenia / Q000378:metabolism*; D012964:Sodium / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D010879:Piperazines; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D012964:Sodium