EXPRESSION CLONING OF A COCAINE-SENSITIVE AND ANTIDEPRESSANT-SENSITIVE HUMAN NORADRENALINE TRANSPORTER

Article

关键词: SK-N-SH;    NOREPINEPHRINE UPTAKE;    TRANSIENT-EXPRESSION;    DNA TRANSFECTION;    ACTIVE UPTAKE;    CELL-LINE;    DOPAMINE;    RECEPTOR;    STORAGE;    INHIBITION;   

DOI  :  10.1038/350350a0

来源: SCIE

【 摘 要 】

AT most synapses, chemical signalling is terminated by a rapid reaccumulation of neurotransmitter into presynaptic terminals 1-5. Uptake systems for the biogenic amines are the initial site of action for therapeutic antidepressants and drugs such as cocaine and the amphetamines. We have isolated a complementary DNA clone encoding a human noradrenaline transporter. The cDNA sequence predicts a protein of 617 amino acids, with 12-13 highly hydrophobic regions compatible with membrane-spanning domains. Expression of the cDNA clone in transfected HeLa cells indicates that noradrenaline transport activity is sodium-dependent and sensitive to selective noradrenaline transport inhibitors. Transporter RNA is localized to the brainstem and the adrenal gland. The predicted protein sequence demonstrates significant amino-acid identity with the Na+/gamma-aminobutyric acid transporter, thus identifying a new gene family for neurotransmitter transporter proteins. Analysis of its structure and function may lead to structure-based drug design for the treatment of human depression and could help determine whether transporter abnormalities underlie affective disorders.

【 授权许可】

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