[3H]GBR-12935 binding to the dopamine transporter is decreased in the caudate nucleus in Parkinson's disease

A. Janowsky, F. Vocci, P. Berger

Research output: Research - peer-reviewArticle

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Abstract

The specific binding of [3H]GBR-12935 to membranes prepared from human caudate nucleus is saturable (B(max) 1.36 ± 0.18 pmol/mg protein), sodium dependent, and of high affinity (K(D) 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.

LanguageEnglish (US)
Pages617-621
Number of pages5
JournalJournal of Neurochemistry
Volume49
Issue number2
StatePublished - 1987
Externally publishedYes

Fingerprint

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

ASJC Scopus subject areas

  • Biochemistry
  • 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, A.; Vocci, F.; Berger, P.

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

Research output: Research - peer-reviewArticle

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AB - The specific binding of [3H]GBR-12935 to membranes prepared from human caudate nucleus is saturable (B(max) 1.36 ± 0.18 pmol/mg protein), sodium dependent, and of high affinity (K(D) 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.

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