Phenylephrine and norepinephrine increase dopamine transporter ligand binding in striatum

Mol Imaging Biol. 2003 Jul-Aug;5(4):217-26. doi: 10.1016/s1536-1632(03)00042-8.

Abstract

Purpose: 8-(2-[18F]fluoroethyl)-2 beta-carbomethoxy-3beta-(4-chlorophenyl)nortropane ([18F]FECNT) is a radiotracer for positron emission tomography (PET) used to trace the location and binding potential (BP) of the dopamine transporter (DAT). We tested the hypothesis that adrenergic receptor agonists increase the BP of [18F]FECNT for the DAT.

Procedures: Anesthetized monkeys were scanned twice to determine the ligand BP at baseline and during administration of phenylephrine (3-6 microg/kg/min) or norepinephrine (0.5-1 microg/kg/min). Standard immunohistochemistry and immunoblot analyses were performed in rats to determine if the quantity of DAT changed with phenylephrine. [18F]FECNT uptake in human embryonic kidney (HEK) cells, stably transfected with DAT cDNA, was measured by gamma scintillation counting during phenylephrine.

Results: The PET measured BP of [18F]FECNT increased by 50% and 45% during the phenylephrine and norepinephrine infusion, respectively. The immunohistochemistry and immunoblot analyses did not show a difference in total DAT.

Conclusion: Adrenergic agonists increase the BP of [18F]FECNT in monkey striatum.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic Agonists
  • Animals
  • Carbon Dioxide / metabolism
  • Corpus Striatum / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Haplorhini / metabolism
  • Humans
  • Ligands
  • Membrane Glycoproteins*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Norepinephrine / metabolism*
  • Phenylephrine / metabolism*
  • Protein Binding
  • Rats
  • Tomography, Emission-Computed

Substances

  • Adrenergic Agonists
  • Dopamine Plasma Membrane Transport Proteins
  • Ligands
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A3 protein, human
  • Slc6a3 protein, rat
  • Carbon Dioxide
  • Phenylephrine
  • Norepinephrine