Phenylephrine and norepinephrine increase dopamine transporter ligand binding in striatum.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
Adrenergic agonists increase the BP of [18F]FECNT in monkey striatum.
D000322:Adrenergic Agonists; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D000882:Haplorhini / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010656:Phenylephrine / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D014055:Tomography, Emission-Computed
D000322:Adrenergic Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; C493216:Slc6a3 protein, rat; D002245:Carbon Dioxide; D010656:Phenylephrine; D009638:Norepinephrine