Desipramine treatment decreases 3H-nisoxetine binding and norepinephrine transporter mRNA in SK-N-SHSY5Y cells.
The antidepressant desipramine has been shown to decrease synaptic membrane concentrations of the norepinephrine re-uptake transporter (NET) in vivo and in vitro, on both an acute and a chronic basis. The possible contribution of decreased NET synthesis to the chronic downregulation of the NETs has not been definitively established. In this study, we treated SK-N-SHSY5Y cells with 100 nM desipramine for 24 or 72 h, and measured 3H-nisoxetine binding (as an estimate of NETs) and NET mRNA by quantitative reverse transcription polymerase chain reaction. Similar to what has been reported previously, membrane 3H-nisoxetine binding was significantly decreased at both 24 and 72 h (approximately 50% at both time points). However, a significant decrease (64 +/- 8% of paired control) of NET mRNA was observed only at the 72-h time point. We conclude that decreased NET synthesis may contribute to the chronic, but not acute, effect of desipramine to downregulate the NET.
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NET NET NETs NETs NET NET NET NET norepinephrine re-uptake transporter norepinephrine transporter desipramine desipramine 3H-nisoxetine 3H-nisoxetine desipramine norepinephrine Desipramine 3H-nisoxetine norepinephrine