Human genetics and pharmacology of neurotransmitter transporters
Lin Z, Madras BK.
Department of Psychiatry, Harvard Medical School,
Division of Neurochemistry,
New England Primate Research Center,
1 Pine Hill Drive, Southborough,
MA 01772-9102, USA.
Handb Exp Pharmacol. 2006;(175):327-71.
ABSTRACTBiogenic amine neurotransmitters are released from nerve terminals and activate pre- and postsynaptic receptors. Released neurotransmitters are sequestered by 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.Pleiotropy
Eugenics before Galton
The literature of eugenics
Germline genetic engineering
Preimplantation genetic diagnosis
A life without pain? Hedonists take note'
Francis Galton and contemporary eugenics
Gene therapy and performance enhancement
and further reading
The Good Drug Guide
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
MDMA: Utopian Pharmacology
Critique of Huxley's Brave New World