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.
Zavosh
A
A
Department of Psychology, University of Washington, Seattle, USA.
Schaefer
J
J
Ferrel
A
A
Figlewicz
D P
DP
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters; D014407:Tumor Cells, Cultured
D018759:Adrenergic Uptake Inhibitors; D002352:Carrier Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; C493227:SLC6A2 protein, human; D027981:Symporters; D005473:Fluoxetine; C011386:nisoxetine; D003891:Desipramine; D009638:Norepinephrine