[125I]RTI‐55 Binding to Cocaine‐Sensitive Dopaminergic and Serotonergic Uptake Sites in the Human Brain

Karley Y. Little, Jacob A. Kirkman, F. Ivy Carroll, George R. Breese, Gary E. Duncan

Research output: Research - peer-reviewArticle

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Abstract

[125I]RTI‐55 is a newly synthesized cocaine congener that may offer advantages over other ligands previously used to examine cocaine binding sites. However, the in vitro pharmacological and anatomical characterization of [125I]RTI‐55 binding sites has not been previously performed in human brain. To determine the specificity, stability, and feasibility of [125I]RTI‐55 for use in radioligand binding assays in postmortem human tissue, a series of experiments were performed characterizing [125I]RTI‐55 binding sites in human brain using homogenized membrane preparations and quantitative autoradtography. Analysis of the association, dissociation, and saturation data favored two‐phase processes. A curve‐fitting analysis of the data derived in saturation experiments found a high‐affinity site with KD= 66 ± 35 pM and Smax= 13.2 ± 10.1 pmol/g of tissue and a low‐affinity site with KD= 1.52 ± 0.55 nM and Bmax of 47.5 ± 11‐2 pmol/g of tissue. Competition by ligands known to bind to the dopamine transporter showed a rank order of RTI‐55 > GBR‐12909 > mazindol > WIN 35428 > = methylphenidate > (−)‐cocaine > buproprion > (±)‐amphetamine. Binding to serotonergic sites was evaluated in the midbrain. Results of the saturation experiment performed autoradiographically in the midbrain showed a single site with KD= 370 ± 84 pM. It appears that [125I]RTI‐55 should be useful in further studies of the regulation of cocaine binding sites using postmortem human specimens.

LanguageEnglish (US)
Pages1996-2006
Number of pages11
JournalJournal of Neurochemistry
Volume61
Issue number6
DOIs
StatePublished - 1993

Fingerprint

Cocaine
Brain
RTI 55
Binding Sites
Tissue
Experiments
Ligands
Mesencephalon
Mazindol
Dopamine Plasma Membrane Transport Proteins
Methylphenidate
Curve fitting
Amphetamine
Assays
Association reactions
Membranes
vanoxerine
Radioligand Assay
Pharmacology
In Vitro Techniques

Keywords

  • Cocaine congener
  • Dopamine transporter
  • Human brain.
  • Serotonin transporter
  • [I]‐RTI‐55

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

[125I]RTI‐55 Binding to Cocaine‐Sensitive Dopaminergic and Serotonergic Uptake Sites in the Human Brain. / Little, Karley Y.; Kirkman, Jacob A.; Carroll, F. Ivy; Breese, George R.; Duncan, Gary E.

In: Journal of Neurochemistry, Vol. 61, No. 6, 1993, p. 1996-2006.

Research output: Research - peer-reviewArticle

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