[3H]GBR‐12935 Binding to the Dopamine Transporter Is Decreased in the Caudate Nucleus in Parkinson's Disease

Aaron Janowsky, Frank Vocci, Paul Berger, Itzchak Angel, Nethanel Zelnik, Joel Kleinman, Phil Skolnick, Steven M. Paul

Research output: Contribution to journalArticle

Abstract

The specific binding of [3H]GBR‐12935 to membranes prepared from human caudate nucleus is saturable (Bmax 1.36 ± 0.18 pmol/mg protein), sodium dependent, and of high affinity (KD 2.34 ± 0.18 nM). Freezing of tissue from rat brain, or refrigeration followed by freezing, results in a small but significant (20%) decrease in specific [3H]GBR‐12935 binding when compared to the binding observed in fresh (nonfrozen) tissue, and this decrease may account, in part, for the differences in specific binding between rat and human brain membranes. Despite small differences in binding site density between fresh and frozen tissue there is a good correlation (r= 0.98; p < 0.01) between the potencies of a series of drugs in displacing specific [3H]GBR‐12935 binding to human caudate membranes and rat striatum as well as in inhibiting dopamine uptake in rat striatal synaptosomes (r= 0.96; p < 0.01). The specific binding of [3H]GBR‐12935 to membranes prepared from the caudate nuclei of patients with Parkinson's disease is decreased compared to membranes prepared from age‐and sex‐matched controls. These data suggest that [3H]GBR‐12935 binds in a sodium‐dependent fashion to the dopamine transport complex in human brain and that specific binding is decreased by a pathological degeneration of dopaminergic neurons to the caudate nucleus.

Original languageEnglish (US)
Pages (from-to)617-621
Number of pages5
JournalJournal of Neurochemistry
Volume49
Issue number2
DOIs
StatePublished - 1987
Externally publishedYes

Fingerprint

Dopamine Plasma Membrane Transport Proteins
Caudate Nucleus
Parkinson Disease
Rats
Membranes
Brain
Tissue
Freezing
Dopamine
Corpus Striatum
Refrigeration
Synaptosomes
Dopaminergic Neurons
Neurons
Sodium
Binding Sites
GBR 12935
Pharmaceutical Preparations
Proteins

Keywords

  • Caudate nucleus
  • Dopamine transport complex
  • Parkinson's disease
  • [H]GBR‐12935

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Cellular and Molecular Neuroscience

Cite this

[3H]GBR‐12935 Binding to the Dopamine Transporter Is Decreased in the Caudate Nucleus in Parkinson's Disease. / Janowsky, Aaron; Vocci, Frank; Berger, Paul; Angel, Itzchak; Zelnik, Nethanel; Kleinman, Joel; Skolnick, Phil; Paul, Steven M.

In: Journal of Neurochemistry, Vol. 49, No. 2, 1987, p. 617-621.

Research output: Contribution to journalArticle

Janowsky, Aaron ; Vocci, Frank ; Berger, Paul ; Angel, Itzchak ; Zelnik, Nethanel ; Kleinman, Joel ; Skolnick, Phil ; Paul, Steven M. / [3H]GBR‐12935 Binding to the Dopamine Transporter Is Decreased in the Caudate Nucleus in Parkinson's Disease. In: Journal of Neurochemistry. 1987 ; Vol. 49, No. 2. pp. 617-621.
@article{8eeae958698340bb9b3e0fedb27a0c04,
title = "[3H]GBR‐12935 Binding to the Dopamine Transporter Is Decreased in the Caudate Nucleus in Parkinson's Disease",
abstract = "The specific binding of [3H]GBR‐12935 to membranes prepared from human caudate nucleus is saturable (Bmax 1.36 ± 0.18 pmol/mg protein), sodium dependent, and of high affinity (KD 2.34 ± 0.18 nM). Freezing of tissue from rat brain, or refrigeration followed by freezing, results in a small but significant (20{\%}) decrease in specific [3H]GBR‐12935 binding when compared to the binding observed in fresh (nonfrozen) tissue, and this decrease may account, in part, for the differences in specific binding between rat and human brain membranes. Despite small differences in binding site density between fresh and frozen tissue there is a good correlation (r= 0.98; p < 0.01) between the potencies of a series of drugs in displacing specific [3H]GBR‐12935 binding to human caudate membranes and rat striatum as well as in inhibiting dopamine uptake in rat striatal synaptosomes (r= 0.96; p < 0.01). The specific binding of [3H]GBR‐12935 to membranes prepared from the caudate nuclei of patients with Parkinson's disease is decreased compared to membranes prepared from age‐and sex‐matched controls. These data suggest that [3H]GBR‐12935 binds in a sodium‐dependent fashion to the dopamine transport complex in human brain and that specific binding is decreased by a pathological degeneration of dopaminergic neurons to the caudate nucleus.",
keywords = "Caudate nucleus, Dopamine transport complex, Parkinson's disease, [H]GBR‐12935",
author = "Aaron Janowsky and Frank Vocci and Paul Berger and Itzchak Angel and Nethanel Zelnik and Joel Kleinman and Phil Skolnick and Paul, {Steven M.}",
year = "1987",
doi = "10.1111/j.1471-4159.1987.tb02908.x",
language = "English (US)",
volume = "49",
pages = "617--621",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - [3H]GBR‐12935 Binding to the Dopamine Transporter Is Decreased in the Caudate Nucleus in Parkinson's Disease

AU - Janowsky, Aaron

AU - Vocci, Frank

AU - Berger, Paul

AU - Angel, Itzchak

AU - Zelnik, Nethanel

AU - Kleinman, Joel

AU - Skolnick, Phil

AU - Paul, Steven M.

PY - 1987

Y1 - 1987

N2 - The specific binding of [3H]GBR‐12935 to membranes prepared from human caudate nucleus is saturable (Bmax 1.36 ± 0.18 pmol/mg protein), sodium dependent, and of high affinity (KD 2.34 ± 0.18 nM). Freezing of tissue from rat brain, or refrigeration followed by freezing, results in a small but significant (20%) decrease in specific [3H]GBR‐12935 binding when compared to the binding observed in fresh (nonfrozen) tissue, and this decrease may account, in part, for the differences in specific binding between rat and human brain membranes. Despite small differences in binding site density between fresh and frozen tissue there is a good correlation (r= 0.98; p < 0.01) between the potencies of a series of drugs in displacing specific [3H]GBR‐12935 binding to human caudate membranes and rat striatum as well as in inhibiting dopamine uptake in rat striatal synaptosomes (r= 0.96; p < 0.01). The specific binding of [3H]GBR‐12935 to membranes prepared from the caudate nuclei of patients with Parkinson's disease is decreased compared to membranes prepared from age‐and sex‐matched controls. These data suggest that [3H]GBR‐12935 binds in a sodium‐dependent fashion to the dopamine transport complex in human brain and that specific binding is decreased by a pathological degeneration of dopaminergic neurons to the caudate nucleus.

AB - The specific binding of [3H]GBR‐12935 to membranes prepared from human caudate nucleus is saturable (Bmax 1.36 ± 0.18 pmol/mg protein), sodium dependent, and of high affinity (KD 2.34 ± 0.18 nM). Freezing of tissue from rat brain, or refrigeration followed by freezing, results in a small but significant (20%) decrease in specific [3H]GBR‐12935 binding when compared to the binding observed in fresh (nonfrozen) tissue, and this decrease may account, in part, for the differences in specific binding between rat and human brain membranes. Despite small differences in binding site density between fresh and frozen tissue there is a good correlation (r= 0.98; p < 0.01) between the potencies of a series of drugs in displacing specific [3H]GBR‐12935 binding to human caudate membranes and rat striatum as well as in inhibiting dopamine uptake in rat striatal synaptosomes (r= 0.96; p < 0.01). The specific binding of [3H]GBR‐12935 to membranes prepared from the caudate nuclei of patients with Parkinson's disease is decreased compared to membranes prepared from age‐and sex‐matched controls. These data suggest that [3H]GBR‐12935 binds in a sodium‐dependent fashion to the dopamine transport complex in human brain and that specific binding is decreased by a pathological degeneration of dopaminergic neurons to the caudate nucleus.

KW - Caudate nucleus

KW - Dopamine transport complex

KW - Parkinson's disease

KW - [H]GBR‐12935

UR - http://www.scopus.com/inward/record.url?scp=0023161727&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023161727&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.1987.tb02908.x

DO - 10.1111/j.1471-4159.1987.tb02908.x

M3 - Article

C2 - 3598589

AN - SCOPUS:0023161727

VL - 49

SP - 617

EP - 621

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 2

ER -