Biogenic amine transporters: regulation in flux

Following vesicular release, the biogenic amine neurotransmitters dopamine, norepinephrine and serotonin are actively cleared from extracellular space s by presynaptic transporters. These transporters interact with multiple ps ychoactive agents including cocaine, amphetamines and antidepressants. Rece nt findings indicate that amine reuptake is likely to be a tightly regulate d component of synaptic plasticity rather than a constitutive determinant o f transmitter clearance. Protein kinase C activation and transporter phosph orylation have been linked to regulatory protein trafficking, and both phos phorylation and trafficking may be influenced by transporter ligands. Recog nition that transmitters, antagonists and second messengers can modify the intrinsic activity, surface expression or protein levels of amine transport ers raises new questions about the fundamental nature of drug actions in vi vo. The theory that dysregulation of transporters may contribute to disease states is supported by the recent discovery that a coding mutation in the human norepinephrine transporter contributes to orthostatic intolerance.