Zavosh A, Schaefer J, Ferrel A, Figlewicz D P
Department of Psychology, University of Washington, Seattle, USA.
Brain Res Bull. 1999 Jul 1;49(4):291-5. doi: 10.1016/s0361-9230(99)00063-5.
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.
抗抑郁药地昔帕明已被证明在体内和体外，无论急性还是慢性给药，均可降低去甲肾上腺素再摄取转运体（NET）的突触膜浓度。NET合成减少对NET慢性下调的可能作用尚未明确确立。在本研究中，我们用100 nM地昔帕明处理SK-N-SHSY5Y细胞24或72小时，并通过定量逆转录聚合酶链反应测量3H-尼索西汀结合（作为NET的估计值）和NET mRNA。与先前报道的结果相似，在24小时和72小时时，膜3H-尼索西汀结合均显著降低（两个时间点均约为50%）。然而，仅在72小时时间点观察到NET mRNA显著降低（配对对照的64±8%）。我们得出结论，NET合成减少可能导致地昔帕明下调NET的慢性作用，但不是急性作用。
