Figure 6.

Structural similarities between NET and DAT confound neuron-specific NE and DA compartmentalization. Both NET and DAT represent the evolutionary divergence of a single catecholamine transporter (meNET), which was isolated and characterized already in the brain of the teleost fish medaka (Roubert et al., 2001). In the light of a strong structural similarity, both NET and DAT take up extracellular DA with a similar potency (A). In fact, in the presence of an excess of extracellular DA (due to either a selective blockade of DAT or a reverted direction of DA transport), this may compete effectively with NE, thus being inappropriately stored within NE terminals. This explains why NE axons may internalize DA in the absence of DAT (Rocha et al., 1998). This same phenomenon also explains why in some instances selective NET inhibitors may paradoxically increase extracellular DA (B). In fact, when a powerful NE release occurs in a densely DA-innervated area, it is very likely that extracellular NE is taken up mostly by fraudulent DA axons instead of authentic NE terminals.