Differential regulation of serotonin-1A receptor-stimulated [35S]GTP gamma S binding in the dorsal raphe nucleus by citalopram and escitalopram.
Differential regulation of serotonin-1A receptor-stimulated [35S]GTP gamma S binding in the dorsal raphe nucleus by citalopram and escitalopram.
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DOI：
10.1016/j.ejphar.2008.01.022
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发表时间：
2008-03
影响因子：
5
通讯作者：
Dania V. Rossi;T. Burke;J. Hensler
中科院分区：
文献类型：
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作者：
Dania V. Rossi;T. Burke;J. Hensler
通过测定5-HT1A受体激动剂(R)-(+)-8-OH-γ(1 nm-10μM)刺激的[35S]GTP-DPAT与S的结合，观察慢性给予西酞普兰或艾司匹兰对中缝背核5-HT1a受体功能的影响。虽然西酞普兰或艾司匹兰的慢性给药被证明能使躯体树突状细胞的5-HT1A自身受体脱敏，但我们发现艾司匹兰治疗降低了5-HT1A受体激活G蛋白的效率，而西酞普兰治疗没有。[~3H]8-OH-DPAT与受体的偶联高亲和力激动剂状态的结合不受这两种处理的影响。有趣的是，通过抑制[~3H]氰基异丙咪胺的结合来衡量，给药导致5-羟色胺转运体的更大的占有率。由于艾司西普兰的结合和作用受限于外消旋西酞普兰中存在的非活性对映体R-西酞普兰，我们认为在受体-G蛋白相互作用水平上调节中缝背核5-HT1A受体的功能可能是艾司西普兰对5-羟色胺转运体的更大抑制的结果。
The effect of chronic citalopram or escitalopram administration on 5-HT1Areceptor function in the dorsal raphe nucleus was determined by measuring [35S]GTPγS binding stimulated by the 5-HT1Areceptor agonist (R)-(+)-8-OH-DPAT (1nM–10 μM). Although chronic administration of citalopram or escitalopram has been shown to desensitize somatodendritic 5-HT1Aautoreceptors, we found that escitalopram treatment decreased the efficacy of 5-HT1Areceptors to activate G proteins, whereas citalopram treatment did not. The binding of [3H]8-OH-DPAT to the coupled, high affinity agonist state of the receptor was not altered by either treatment. Interestingly, escitalopram administration resulted in greater occupancy of serotonin transporter sites as measured by the inhibition of [3H]cyanoimipramine binding. As the binding and action of escitalopram is limited by the inactive enantiomer R-citalopram present in racemic citalopram, we propose that the regulation of 5-HT1Areceptor function in the dorsal raphe nucleus at the level of receptor-G protein interaction may be a result of greater inhibition of the serotonin transporter by escitalopram.