title: Selective labeling of the dopamine transporter by the high affinity ligand 3 beta-(4-[125I]iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester.
abstract: The iodine-125 analog of the dopaminergically selective cocaine analog 3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester (RT1-121) was evaluated as a probe for the dopamine transporter in rat striatum. Saturation and kinetic studies indicated that [125I]RTI-121 binds to both high and low affinity components. The Kd of the high affinity component was 0.14 +/- 0.01 nM (mean +/- standard error), whereas the low affinity component demonstrated an affinity of 1.59 +/- 0.09 nM. The corresponding numbers of striatal binding sites labeled by [125I]RTI-121 were 295 +/- 6 and 472 +/- 59 pmol/g of tissue (original wet weight), respectively. Intrastriatal injections of 6-hydroxydopamine eliminated > 90% of specific [125I]RTI-121 binding in the striatum. The pharmacological profile of specific [125I]RTI-121 binding in the rat striatum was consistent with that of the dopamine transporter. There was a strong (r = 0.98, p < 0.0001) correlation between the potencies of drugs that displaced specific [125I]RTI-121 binding and the potencies of these drugs to inhibit the uptake of [3H]dopamine. In contrast, no correlation was found for the potencies of drugs to inhibit the uptake of either [3H]norepinephrine or [3H]serotonin. Autoradiographs produced using [125I]RTI-121 demonstrated a distribution of label consistent with the distribution of dopaminergic neurons in rat brain. Because of its high affinity and high selectivity for the dopamine transporter, [125I]RTI-121 may be an extremely useful ligand for the dopamine transporter.
authors.affiliation: Molecular Pharmacology Section, National Institutes of Health/National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland 21224, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Boja
authors.forename: J L
authors.initials: JL
authors.lastname: Cadet
authors.forename: T A
authors.initials: TA
authors.lastname: Kopajtic
authors.forename: J
authors.initials: J
authors.lastname: Lever
authors.forename: H H
authors.initials: HH
authors.lastname: Seltzman
authors.forename: C D
authors.initials: CD
authors.lastname: Wyrick
authors.forename: A H
authors.initials: AH
authors.lastname: Lewin
authors.forename: P
authors.initials: P
authors.lastname: Abraham
authors.forename: F I
authors.initials: FI
authors.lastname: Carroll
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D007700:Kinetics; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; C079213:RTI 121; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D003042:Cocaine; D004298:Dopamine