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Human Genetics and Pharmacology of Neurotransmitter Transporters

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Neurotransmitter Transporters

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 175))

Abstract

Biogenic amine neurotransmitters are released from nerve terminals and activate pre-andpostsynaptic receptors. Released neurotransmitters are sequesteredby transporters into presynaptic neurons, a major mode of their inactivation in the brain. Genetic studies of human biogenic amine transporter genes, including the dopamine transporter (hDAT; SLC6A3), the serotonin transporter (hSERT; SLC6A4), and the norepinephrine transporter (hNET; SLC6A2) have provided insight into how genomic variations in these transporter genes influence pharmacology and brain physiology. Genetic variants can influence transporter function by various mechanisms, including substrate affinities, transport velocity, transporter expression levels (density), extracellular membrane expression, trafficking and turnover, and neurotransmitter release. It is increasingly apparent that genetic variants of monoamine transporters also contribute to individual differences in behavior and neuropsychiatric disorders. This chapter summarizes current knowledge of transporters with a focus on genomic variations, expression variations, pharmacology of protein variants, and known association with human diseases.

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Authors and Affiliations

  1. Department of Psychiatry, Harvard Medical School, Division of Neurochemistry, New England Primate Research Center, 1 Pine Hill Drive, Southborough, MA, 01772-9102, USA

    Z. Lin & B. K. Madras

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  1. Z. Lin
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  2. B. K. Madras
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  1. Institute of Pharmacology Center for Biomolecular Medicine and Pharmacology, Medical University Vienna, Waehringer Str. 13a, A-1090, Wien, Austria

    Harald H. Sitte  & Michael Freissmuth  & 

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Lin, Z., Madras, B.K. (2006). Human Genetics and Pharmacology of Neurotransmitter Transporters. In: Sitte, H.H., Freissmuth, M. (eds) Neurotransmitter Transporters. Handbook of Experimental Pharmacology, vol 175. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-29784-7_16

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