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

J Neurochem. 1986 Apr;46(4):1272-6. 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.

Publication types

  • Comparative Study

MeSH terms

  • 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


  • Cations
  • Dopamine Antagonists
  • Hydroxydopamines
  • Ligands
  • Piperazines
  • Tritium
  • Oxidopamine
  • 1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine
  • Sodium
  • Dopamine