Specific in vitro binding of (S,S)-[3H]MeNER to norepinephrine transporters.
The aim of this study was to determine the selectivity of (S,S)-2-(alpha-(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 approximately 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.
Ghose
Subroto
S
Molecular Imaging Branch, NIMH, NIH, Bethesda, Maryland 20892, USA. subroto.ghose@UTSouthwestern.edu
Fujita
Masahiro
M
Morrison
Paul
P
Uhl
George
G
Murphy
Dennis L
DL
Mozley
P David
PD
Schou
Magnus
M
Halldin
Christer
C
Innis
Robert
R
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology; D003164:Competitive Bidding / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout / Q000502:physiology; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010636:Phenols / Q000737:chemistry / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D019275:Radiopharmaceuticals / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D027981:Symporters / Q000172:deficiency / Q000378:metabolism*; D014018:Tissue Distribution
D015283:Citalopram; D005473:Fluoxetine; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010636:Phenols; D010879:Piperazines; D019275:Radiopharmaceuticals; D017367:Selective Serotonin Reuptake Inhibitors; D027981:Symporters; C493228:Slc6a2 protein, mouse; C011386:nisoxetine; C002383:morpholinomethylphenol; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine