Amine Transporters

Abstract

Amine transporters in plasma membranes mediate the transport of dopamine, (nor)adrenaline ((nor)epinephrine) and serotonin. These transporters are members of the larger Na+‐ and Cl‐dependent neurotransmitter transporters.

Keywords: dopamine; noradrenaline; norepinephrine; serotonin; sodium; chloride

Figure 1.

Amine transporters in plasma membranes and in membranes of storage vesicles. The amine transporter in the plasma membrane transports amine (A) from the extracellular space into the cytoplasm, with cotransport of Na+ and Cl. This uptake is driven by the inwardly directed Na+ gradient and outwardly directed K+ gradient, maintained by Na+/K+ adenosine triphosphatase (ATPase). Uptake of dopamine and noradrenaline, but not of serotonin, is also promoted by the membrane potential, negative inside. In contrast, the vesicular amine transporter (VAT) takes up A with countertransport of H+, and the high intravesicular H+ concentration is maintained by the ATP‐dependent H+ pump or H+‐transporting ATPase (HT ATPase). On the postsynaptic side, an amine receptor is depicted coupled to G protein subunits.

Figure 2.

Proposed topology of plasma membrane amine transporters. The large extracellular loop between transmembrane domains 3 and 4 have two to four consensus sites for glycosylation (ψ), whereas consensus sites for phosphorylation by PKA (A), PKC (C) or Ca2+–calmodulin‐dependent kinase II (KII) are found on the amino and carboxy tails as well as on the second intracellular loop.

Figure 3.

Translocation cycle. Starting at the lower left and continuing counterclockwise, the transporter facing outward binds Na+, Cl and amine (A). A conformational change occurs bringing the transporter in a form facing inward (top right‐hand corner) allowing the dissociation of Na+, Cl and A. The empty, inward‐facing, transporter undergoes the reorientation step (top left to bottom left), which in the case of the serotonin transporter is promoted by K+. The transporter is now ready for a new translocation cycle.

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Further Reading

Amara SA (ed.) (1998) Neurotransmitter transporters. Methods in Enzymology 296: 1–730.

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Lin Z, Wang W and Uhl GR (2000) Dopamine transporter tryptophan mutants highlight candidate dopamine‐ and cocaine‐selective domains. Molecular Pharmacology 58: 1581–1592.

Reith MEA (ed.) (2002) Neurotransmitter Transporters: Structure, Function and Regulation, 2nd edn. Totowa, NJ: Humana Press.

Reith MEA (guest ed.) (2003) Transporters as targets for drugs and endogenous compounds. European Journal of Pharmacology, (Special Issue) Vol. 479, Nos. 1–3.

Robinson MB (2002) Regulated trafficking of neurotransmitter transporters: common notes but different melodies. Journal of Neurochemistry 80: 1–11.

Roubert C, Cox PJ, Brüss M, et al. (2001) Determination of residues in the norepinephrine transporter that are critical for tricyclic antidepressant affinity. Journal of Biological Chemistry 276: 8254–8260.

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How to Cite close
Zhen, Juan, and Reith, Maarten EA(Sep 2005) Amine Transporters. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0004091]