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Structure, function and regulation of the 5-hydroxytryptamine (serotonin) transporter.

The serotonin transporter (SERT), which terminates serotonergic neurotransmission by rapid re-uptake of 5-hydroxytryptamine (5-HT) back into the nerve terminal was the subject of two studies. First, the regulatory effects of antidepressants on the expression of SERT was investigated. After chronic exposure of SERT to antidepressants, substrate transport and antidepressant binding parameters were determined. Long-term exposure of SERT to a selective 5-HT-re-uptake inhibitor, citalopram, resulted in the down-regulation of the expression level. The observed effects depend on drug concentration and exposure time and are reversible. Basal uptake levels could be regained 48 h after cessation of the treatment. Secondly, in order to gain insight into the molecular mechanism of substrate transport, potential interactions of SERT with the noradrenaline transporter (NET) have been investigated. A chimeric concatameric transporter construct consisting of rat SERT and rat NET has been cloned and characterized pharmacologically in a heterologous expression system.