The Extraneuronal Monoamine Transporter Exists in Human Central Nervous System Glia

https://doi.org/10.1016/S1054-3589(08)60764-4Get rights and content

Publisher Summary

Research shows that the extraneuronal monoamine transporter exists in cells that stem from human central nervous system (CNS) glia. The physiological role of the extraneuronal monoamine transporter in the CNS may be characterized by a second line of defense. It inactivates that fraction of monoamines that escapes neuronal re-uptake and thus prevents uncontrolled spreading of the signal. Also, from various studies on sympathetically innervated peripheral organs, it is well known that both the neuronal type of noradrenaline transporter (uptake1) and the extraneuronal monoamine transporter (uptake2) are important for the inactivation of released catecholamines. The extraneuronal monoamine transporter operates independently of the Na+ gradient. It is, at least partially, driven by the membrane potential and is sensitive to corticosterone. In the CNS, the close proximity between catecholaminergic neurons and glia cells raises the question whether the extraneuronal monoamine transporter contributes to the inactivation of centrally released catecholamines. There is strong evidence in support of the view that glia cells accumulate monoamines by a saturable transport system; the underlying mechanism, however, is still under research. Two developments have opened the possibility to readdress this question. These are: the isocyanines and pseudoisocyanines represent a novel class of selective and extremely potent inhibitors of the extraneuronal monoamine transporter, and the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) turned out to be an excellent substrate of the extraneuronal monoamine transporter that is superior to noradrenaline for in vitro studies.

References (5)

  • H. Kimelberg et al.

    High affinity uptake of [3H]norepinephrine by primary astrocyte cultures and its inhibition by tricyclic antidepressants

    J. Neurochem

    (1983)
  • L.A. Paterson et al.

    Sodium-independent transport of noradrenaline in mouse and rat astrocytes in primary culture

    J. Neurosci. Res

    (1989)
There are more references available in the full text version of this article.

Cited by (24)

  • Evidence for significant contribution of a newly identified monoamine transporter (PMAT) to serotonin uptake in the human brain

    2007, Biochemical Pharmacology
    Citation Excerpt :

    Transporter-mediated cellular uptake plays a key role in determining the intensity and duration of 5-HT signaling [4,7]. Earlier studies suggested that two different transport systems for 5-HT may exist, a high affinity-low capacity process and a low affinity-high capacity process, which are termed uptake1 and uptake2, respectively [8–10]. The uptake1 system for 5-HT is now known to be mediated by the Na+/Cl−-dependent, high affinity transporter, SERT.

  • Dopamine, Immunity, and Disease

    2023, Pharmacological Reviews
View all citing articles on Scopus
View full text