title: MPTP lesions of the nigrostriatal dopaminergic projection decrease [3H]1-[1-(2-thienyl)cyclohexyl]piperidine binding to PCP site 2: further evidence that PCP site 2 is associated with the biogenic amine reuptake complex.
abstract: Our previous studies have demonstrated that, using membranes of guinea pig brain, [3H]1-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) labels not only the phencyclidine binding site associated with the NMDA receptor (PCP site 1), but also a second high affinity binding site which is associated with the biogenic amine reuptake carrier (termed PCP site 2). To test this hypothesis, the binding of [3H]GBR12935 to the dopamine transporter, and [3H]TCP binding to PCP sites 1 and 2 were measured in caudates harvested from control, MPTP-treated and reserpine-treated dogs. MPTP treatment decreased dopamine levels by over 99%, decreased [3H]GBR12935 binding by over 90%, decreased [3H]TCP binding to PCP site 2 by about 50%, and had no significant effect on [3H]TCP binding to PCP site 1. These data are consistent with the hypothesis that a portion of PCP site 2 is associated with dopaminergic nerve terminals in dog caudate.
authors.affiliation: Laboratory of Medicinal Chemistry, NIDDK, Bethesda, MD 20892.
authors.forename: H C
authors.initials: HC
authors.lastname: Akunne
authors.forename: J N
authors.initials: JN
authors.lastname: Johannessen
authors.forename: B R
authors.initials: BR
authors.lastname: de Costa
authors.forename: K C
authors.initials: KC
authors.lastname: Rice
authors.forename: R B
authors.initials: RB
authors.lastname: Rothman
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects*; D004285:Dogs; D004298:Dopamine / Q000502:physiology; D005260:Female; D009434:Neural Pathways / Q000187:drug effects; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D017478:Receptors, Phencyclidine; D012110:Reserpine / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects*
chemical_list: D001679:Biogenic Amines; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D012110:Reserpine; C012058:tenocyclidine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D010622:Phencyclidine; D004298:Dopamine