title: Characterization of sodium-dependent [3H]GBR-12935 binding in brain: a radioligand for selective labelling of the dopamine transport complex.
abstract: 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.
authors.forename: A
authors.initials: A
authors.lastname: Janowsky
authors.forename: P
authors.initials: P
authors.lastname: Berger
authors.forename: F
authors.initials: F
authors.lastname: Vocci
authors.forename: R
authors.initials: R
authors.lastname: Labarca
authors.forename: P
authors.initials: P
authors.lastname: Skolnick
authors.forename: S M
authors.initials: SM
authors.lastname: Paul
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002412:Cations; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D006892:Hydroxydopamines / Q000494:pharmacology; D008024:Ligands; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism; D016627:Oxidopamine; D010879:Piperazines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology*; D013570:Synaptic Membranes / Q000378:metabolism*; D014018:Tissue Distribution; D014316:Tritium
chemical_list: D002412:Cations; D018492:Dopamine Antagonists; D006892:Hydroxydopamines; D008024:Ligands; D010879:Piperazines; D014316:Tritium; D016627:Oxidopamine; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D012964:Sodium; D004298:Dopamine