The Extraneuronal Monoamine Transporter Exists in Human Central Nervous System Glia

Abstract

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 (uptake 1 ) and the extraneuronal monoamine transporter (uptake 2 ) 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.