Characterization of sodium-dependent [3H]GBR-12935 binding in brain: a radioligand for selective labelling of the dopamine transport complex

• Published in: Journal of neurochemistry Vol. 46; no. 4; p. 1272
• Main Authors: Janowsky, A, Berger, P, Vocci, F, Labarca, R, Skolnick, P, Paul, S M
• Format: Journal Article
• Language: English
• Published: England 01.04.1986
• Subjects: Animals; Binding Sites - drug effects; Biological Transport; Brain - metabolism; Cations; Corpus Striatum - metabolism; Dopamine - metabolism; Dopamine Antagonists; Hydroxydopamines - pharmacology; Ligands; Male; Nucleus Accumbens - metabolism; Oxidopamine; Piperazines - metabolism; Rats; Rats, Inbred Strains; Sodium - pharmacology; Synaptic Membranes - metabolism; Tissue Distribution; Tritium
• ISSN: 0022-3042
• DOI: 10.1111/j.1471-4159.1986.tb00649.x

High-affinity and saturable binding sites for the diphenyl-substituted piperazine derivative [3H]GBR-12935 have been characterized in crude synaptosomal membranes prepared from rat brain. The specific binding of [3H]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 [3H]GBR-12935 binding in all other brain areas was 10% or less of the binding found in the striatum. The affinity of [3H]GBR-12935 for binding sites in the striatum is increased in the presence of Na+ but other cations, including K+, Ca2+, or Mg2+, inhibit specific binding. There is an excellent correlation (r = 0.96, p less than 0.01) between the potencies of a series of drugs in inhibiting [3H]GBR-12935 binding to striatal membranes and their potencies in inhibiting [3H]3,4-dihydroxyphenylethylamine ([3H]dopamine) uptake in synaptosomes. Agonists and antagonists of other neurotransmitter receptor or drug recognition sites have little or no effect on specific [3H]GBR-12935 binding to striatal membranes. In addition, prior intracerebroventricular administration of 6-hydroxydopamine results in a decrease in the number of specific [3H]GBR-12935 binding sites in the striatum. These data indicate that [3H]GBR-12935 is a selective radioligand of the presynaptic dopamine transport complex in brain.