Selective labeling of the dopamine transporter by the high affinity ligand 3β-(4-[125I]iodophenyl)tropane-2β-carboxylic acid isopropyl ester

J. W. Boja, J. L. Cadet, T. A. Kopajtic, J. Lever, H. H. Seltzman, C. D. Wyrick, A. H. Lewin, P. Abraham, F. I. Carroll

Research output: Contribution to journalArticle

Abstract

The iodine-125 analog of the dopaminergically selective cocaine analog 3β-(4-iodophenyl)tropane-2β-carboxylic acid isopropyl ester (RTI-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 K(d) 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.

Original languageEnglish (US)
Pages (from-to)779-786
Number of pages8
JournalMolecular Pharmacology
Volume47
Issue number4
StatePublished - May 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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    Boja, J. W., Cadet, J. L., Kopajtic, T. A., Lever, J., Seltzman, H. H., Wyrick, C. D., Lewin, A. H., Abraham, P., & Carroll, F. I. (1995). Selective labeling of the dopamine transporter by the high affinity ligand 3β-(4-[125I]iodophenyl)tropane-2β-carboxylic acid isopropyl ester. Molecular Pharmacology, 47(4), 779-786.