Serotonin 5‐HT2C Receptor RNA Editing Alters Receptor Basal Activity
Serotonin 5‐HT2C Receptor RNA Editing Alters Receptor Basal Activity
复制标题
5-羟色胺 5-HT2C 受体 RNA 编辑改变受体基础活性
DOI：
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发表时间：
1999
影响因子：
4.7
通讯作者：
C. Niswender
中科院分区：
文献类型：
--
作者：
K. Herrick‐Davis;E. Grinde;C. Niswender
摘要：对大鼠和人5-HT2C受体亚型的激动剂非依赖性激活COS-7细胞产生的磷酸肌醇进行了研究。未编辑的异构体(5-HT2C-INI)显示出最大的基础活性，刺激肌醇磷酸的产生是完全编辑的异构体(5-HT2C-VGV)的四倍。所有测试的其他亚型都显示出中等水平的基础活性。受体表达水平降低50%会导致基础活性的平行下降。5-羟色胺通过5-HT2C-INI受体刺激基础水平的肌醇磷酸生成是基础水平的两倍，通过5-HT2C-VGV受体刺激基础水平的八倍，但产生相似的最大水平的肌醇磷酸。5-羟色胺与5-HT2C-INI结合最符合双位点模型，KH=7.6 nM，KL=160 nM，而5-HT2C-VGV与5-HT2C-VGV最符合单位点模型，KI=163 nM。[~3H]-Mesulergine标记的5-HT2C-INI受体占总受体的36%，而5-HT2C-VGV受体仅占12%。[3H]5-HT2C-INI的5-HTKd值从5.1 nM增加到20 nM。[~3H]两种异构体的Mesulergine Kd值相同。生产肌醇磷酸的5-HTEC50值从5-HT2C-INI的6.1 nM增加到5-HT2C-VGV的30 nM。这些结果表明，RNA编辑降低了5-HT2C受体的基础活性、激动剂亲和力和效力，表明RNA编辑可能在调节5-羟色胺能信号转导和对药物治疗的反应中发挥作用。
Abstract : Rat and human serotonin 5‐HT2C receptor isoforms were evaluated for agonist‐independent activation of inositol phosphate production in COS‐7 cells. The nonedited isoform (5‐HT2C‐INI) displayed the greatest basal activity, stimulating inositol phosphate production fourfold over the fully edited isoform (5‐HT2C‐VGV). All of the other isoforms tested displayed intermediate levels of basal activity. Decreasing receptor expression levels by 50% produced a parallel decrease in basal activity. 5‐HT stimulated inositol phosphate production twofold over basal levels through the 5‐HT2C‐INI receptor and eightfold over basal levels through the 5‐HT2C‐VGV receptor but produced similar maximal levels of inositol phosphate. 5‐HT competition for [3H]mesulergine binding to 5‐HT2C‐INI best fit a two‐site analysis with KH = 7.6 nM and KL = 160 nM, whereas 5‐HT2C‐VGV best fit a one‐site model with Ki = 163 nM. [3H]5‐HT labeled 36% of the total population of 5‐HT2C‐INI receptors labeled by [3H]‐mesulergine but only 12% of 5‐HT2C‐VGV receptors. [3H]5‐HT KD values increased from 5.1 nM for 5‐HT2C‐INI to 20 nM for 5‐HT2C‐VGV. [3H]Mesulergine KD values were the same for both isoforms. 5‐HT EC50 values for inositol phosphate production increased from 6.1 nM for 5‐HT2C‐INI to 30 nM for 5‐HT2C‐VGV. These results demonstrate that RNA editing decreases 5‐HT2C receptor basal activity, agonist affinity, and potency, indicating that RNA editing may play a role in regulating serotonergic signal transduction and response to drug therapy.
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DOI：
10.1016/s0021-9258(18)53442-6
发表时间：
1993-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
P. Samama;S. Cotecchia;T. Costa;R. Lefkowitz
通讯作者：
P. Samama;S. Cotecchia;T. Costa;R. Lefkowitz
影响因子：
3.6
作者：
R. Westphal;J. Backstrom;E. sanders-Bush
通讯作者：
R. Westphal;J. Backstrom;E. sanders-Bush
影响因子：
3.6
作者：
Berg, KA;Maayani, S;Clarke, WP
通讯作者：
Clarke, WP
影响因子：
56.9
作者：
CHEN, SH;HABIB, G;CHAN, L
通讯作者：
CHAN, L
5-羟色胺2C 受体激活通过花生四烯酸代谢抑制5-羟色胺1B 样受体功能。
影响因子：
3.6
作者：
Berg,KA;Maayani,S;Clarke,WP
通讯作者：
Clarke,WP