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  • Title: [Pharmacology of monoamine neurotransmitter transporters].
    Author: Dohi T, Kitayama S, Kumagai K, Hashimoto W, Morita K.
    Journal: Nihon Yakurigaku Zasshi; 2002 Nov; 120(5):315-26. PubMed ID: 12491807.
    Abstract:
    Following exocytotic release, the biogenic amine neurotransmitters, norepinephrine, dopamine, and serotonin are removed from the synaptic cleft by the respective transporter, NET, DAT, and SERT, located on the plasma membrane and then re-stored into synaptic vesicles by vesicular monoamine transporter, VMAT. The molecular cloning of these transporters revealed that NET, DAT, and SERT are members of a sodium-dependent neurotransmitter transporter gene family, while VMATs arise from proton-dependent transporter gene family. Structural features common to NET, DAT, and SERT reveal a putative 12 transmembrane-spanning domain structure with cytosolic N- and C-terminal regions. Recent evidence suggest the regulation of the functional expression of these transporters via phosphorylation, which include direct phosphorylation of transporter proteins and/or of associated proteins that may control transporter function/expression. In addition, the substrates and inhibitors for these transporters appear capable of regulating transporter cell surface expression, thereby suggesting both activity-dependent and pharmacological regulatory mechanisms for transporter expression. Analyses of the genes provide new insight into their relation to neuronal diseases since NET, DAT and SERT are the molecular targets for many antidepressants as well as drugs of abuse such as cocaine and amphetamine. The availability of cDNAs of these and vesicular transporters has permitted detailed pharmacological studies in heterologous expression systems, and thus would promise the development of novel drugs with diverse chemical structures.
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