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Norepinephrine transporter expression and function in noradrenergic cell differentiation.

M Sieber-Blum1, Z Ren

  • 1Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee 53226, USA.

Molecular and Cellular Biochemistry
|December 7, 2000
PubMed
Summary
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Norepinephrine transporter (NET) is present in early embryonic development and regulates noradrenergic neuron differentiation. Inhibiting NET can disrupt this crucial process in both the central and peripheral nervous systems.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Molecular Biology

Background:

  • The classical function of norepinephrine transporter (NET) is norepinephrine (NE) re-uptake by mature neurons.
  • NET expression and function during embryonic development are not fully understood.

Purpose of the Study:

  • To investigate the role of NET in early embryonic development.
  • To determine how growth factors influence NET expression and function.
  • To examine the effect of NE transport on noradrenergic neuron differentiation.

Main Methods:

  • Review of previous data and presentation of new results.
  • Analysis of NET expression in various embryonic tissues.
  • Studies on cultured quail neural crest cells and presumptive locus ceruleus (LC) cells.

Related Experiment Videos

  • Investigation of growth factor regulation (FGF-2, NT-3, TGF-beta1) on NET mRNA and function.
  • Assessment of norepinephrine uptake inhibitors' effects on differentiation.

    • Main Results:

    • NET is expressed in a wide range of neuronal and non-neuronal tissues during early embryonic development.
    • Fibroblast growth factor-2, neurotrophin-3, and transforming growth factor-beta1 increase NET mRNA and promote NET function in neural crest and LC cells.
    • Norepinephrine transport regulates the differentiation of noradrenergic neurons by promoting tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) expression.
    • Norepinephrine uptake inhibitors (desipramine, cocaine) inhibit noradrenergic differentiation.

    Conclusions:

    • NET plays a significant role beyond re-uptake during embryonic development.
    • Norepinephrine transport is critical for establishing the noradrenergic phenotype in the peripheral and central nervous systems.
    • Inhibitors of norepinephrine uptake can adversely affect noradrenergic cell differentiation in the sympathetic ganglion and LC.