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Phenylephrine and norepinephrine increase dopamine transporter ligand binding in striatum
Michael Byas-Smith1, John Votaw, Jian Hua
1Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia 30022, USA. michael_byas-smith@emoryhealthcare.org
Molecular Imaging and Biology
|September 23, 2003
Summary
Adrenergic agonists, like phenylephrine and norepinephrine, significantly increase the binding potential of the dopamine transporter radiotracer [18F]FECNT in monkeys. This PET imaging study reveals a key interaction affecting dopamine transporter availability.
Area of Science:
- Neuroscience
- Radiochemistry
- Pharmacology
Background:
- The dopamine transporter (DAT) is crucial for regulating dopaminergic neurotransmission.
- Positron emission tomography (PET) radiotracers like 8-(2-[18F]fluoroethyl)-2 beta-carbomethoxy-3beta-(4-chlorophenyl)nortropane ([18F]FECNT) enable in vivo quantification of DAT.
- Understanding factors influencing DAT binding potential (BP) is essential for interpreting PET studies.
Purpose of the Study:
- To investigate whether adrenergic receptor agonists can modulate the binding potential of [18F]FECNT for the DAT.
- To test the hypothesis that phenylephrine or norepinephrine administration alters [18F]FECNT BP in vivo.
Main Methods:
- PET scans were performed on anesthetized monkeys to measure baseline [18F]FECNT BP.
- BP was re-assessed during intravenous infusions of phenylephrine or norepinephrine.
- Immunohistochemistry and immunoblotting in rats examined DAT quantity changes; [18F]FECNT uptake was measured in DAT-transfected HEK cells.
Main Results:
- PET imaging demonstrated a substantial increase in [18F]FECNT BP by 50% with phenylephrine and 45% with norepinephrine.
- No significant changes in total DAT quantity were observed in rat brain tissue.
- [18F]FECNT uptake in HEK cells did not change with phenylephrine exposure.
Conclusions:
- Adrenergic agonists, specifically phenylephrine and norepinephrine, enhance the binding potential of [18F]FECNT for DAT in the primate striatum.
- The observed increase in BP is likely due to altered tracer kinetics or receptor interactions rather than changes in DAT expression levels.