Specific in vitro binding of (S,S)-[3H]MeNER to norepinephrine transporters

Subroto Ghose, Masahiro Fujita, Paul Morrison, George Uhl, Dennis L. Murphy, P. David Mozley, Magnus Schou, Christer Halldin, Robert Innis

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The aim of this study was to determine the selectivity of (S,S)-2-(α-(2-methoxyphenoxy)benzyl)morpholine (MeNER) binding to norepinephrine transporters (NET). Quantitative autoradiography studies of NET binding were performed in brains of wildtype mice and those of mutant mice lacking one or two alleles of the NET gene. [3H]MeNER binding in the wildtype mouse brains was consistent with previously reported distributions of NET. Highest levels were found in the locus coeruleus, thalamus, hypothalamus, and bed nucleus of stria terminalis. Specific binding in these regions was ∼50% in the heterozygous NET mice and negligible in the NET knockout mice. Binding in the wildtype mouse brains was displaced by the NET ligand, nisoxetine, but not by the serotonin or dopamine transporter blockers, citalopram or GBR 12935. [3H]MeNER displayed much higher affinity for NET than for SERT or DAT in homogenate binding studies. Each of these features supports the binding specificity of this candidate in vivo NET ligand.

Original languageEnglish (US)
Pages (from-to)100-104
Number of pages5
JournalSynapse
Volume56
Issue number2
DOIs
StatePublished - May 1 2005

Keywords

  • Autoradiography
  • Binding assay
  • Knockout mice
  • NET

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Ghose, S., Fujita, M., Morrison, P., Uhl, G., Murphy, D. L., Mozley, P. D., Schou, M., Halldin, C., & Innis, R. (2005). Specific in vitro binding of (S,S)-[3H]MeNER to norepinephrine transporters. Synapse, 56(2), 100-104. https://doi.org/10.1002/syn.20133