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Characterization of Sodium‐Dependent [ 3 H]GBR‐12935 Binding in Brain: A Radioligand for Selective Labelling of the Dopamine Transport Complex
Author(s) -
Janowsky Aaron,
Berger Paul,
Vocci Frank,
Labarca Rodrigo,
Skolnick Phil,
Paul Steven M.
Publication year - 1986
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1986.tb00649.x
Subject(s) - radioligand , striatum , chemistry , dopamine , dopamine plasma membrane transport proteins , nucleus accumbens , binding site , biochemistry , biophysics , dopamine transporter , receptor , biology , endocrinology , transporter , gene
High‐affinity and saturable binding sites for the diphenyl‐substituted piperazine derivative [ 3 H]GBR‐12935 have been characterized in crude synaptosomal membranes prepared from rat brain. The specific binding of [ 3 H]GBR‐12935 is sodium‐dependent and is unevenly distributed among various brain regions, with the highest concentration of binding sites being found in the corpus striatum and nucleus accumbens. Sodium‐dependent [ 3 H]GBR‐12935 binding in all other brain areas was 10% or less of the binding found in the striatum. The affinity of [ 3 H]GBR‐12935 for binding sites in the striatum is increased in the presence of Na + but other cations, including K + , Ca 2+ , or Mg 2+ , inhibit specific binding. There is an excellent correlation ( r = 0.96, p < 0.01) between the potencies of a series of drugs in inhibiting [ 3 H]GBR‐12935 binding to striatal membranes and their potencies in inhibiting [ 3 H]3,4‐dihydroxyphenylethylamine ([ 3 H]dopamine) uptake in synaptosomes. Agonists and antagonists of other neurotransmitter receptor or drug recognition sites have little or no effect on specific [ 3 H]GBR‐12935 binding to striatal membranes. In addition, prior intracerebroventricular administration of 6‐hydroxydopamine results in a decrease in the number of specific [ 3 H]GBR‐12935 binding sites in the striatum. These data indicate that [ 3 H]GBR‐12935 is a selective radioligand of the presynaptic dopamine transport complex in brain.