Selective 5-HT1D alpha serotonin receptor gene expression in trigeminal ganglia: implications for antimigraine drug development.
Selective 5-HT1D alpha serotonin receptor gene expression in trigeminal ganglia: implications for antimigraine drug development.
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三叉神经节中选择性 5-HT1D α 血清素受体基因表达：对抗偏头痛药物开发的影响。
DOI：
10.1073/pnas.91.9.3666
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发表时间：
1994
影响因子：
11.1
通讯作者：
Moskowitz,MA
中科院分区：
文献类型：
--
作者：
Rebeck,GW;Maynard,KI;Hyman,BT;Moskowitz,MA
药理学数据表明，抗偏头痛药物如舒马曲坦的作用可能是由三叉神经血管神经末梢上的5-HT 1D样5-羟色胺受体介导的。我们使用与5-HT 1B/D家族（人5-HT 1D α和5-HT 1D β;大鼠5-HT 1B）编码序列唯一同源的寡核苷酸进行聚合酶链反应，寻找编码豚鼠和人三叉神经节中5-HT 1D受体亚型的mRNA表达的分子证据。在豚鼠三叉神经节样品中观察到预测大小的单一条带;序列分析显示存在单一信息，与人5-HT 1D α和5-HT 1D β受体DNA序列分别具有85%和71%的相同性。对人类死后三叉神经节的类似分析显示，5-HT 1D α受体信息的存在，而不是5-HT 1D β受体信息。由于最近的一份报告发现，仅编码5-HT 1D β受体亚型的mRNA由中枢神经系统的血管平滑肌表达，本研究结果表明，开发选择性5-HT 1D α受体激动剂作为降低心肌梗死和可能的中风风险的策略的重要性，所述心肌梗死和中风使偏头痛的急性治疗复杂化。
Pharmacological data suggest that the actions of antimigraine drugs such as sumatriptan may be mediated by 5-HT1D-like serotonin receptors on trigeminovascular nerve endings. We sought molecular evidence for the expression of an mRNA species encoding the 5-HT1D receptor subtype in guinea pig and human trigeminal ganglia, using the polymerase chain reaction with oligonucleotides uniquely homologous to the coding sequences of the 5-HT1B/D family (human 5-HT1D alpha and 5-HT1D beta; rat 5-HT1B). A single band of predicted size was observed in samples from guinea pig trigeminal ganglia; sequence analysis revealed the presence of a single message, which was 85% and 71% identical to the human 5-HT1D alpha and 5-HT1D beta receptor DNA sequences, respectively. Similar analyses of postmortem human trigeminal ganglia revealed the presence of 5-HT1D alpha, but not 5-HT1D beta, receptor message. Inasmuch as one recent report found that mRNA encoding only the 5-HT1D beta receptor subtype was expressed by vascular smooth muscle of the central nervous system, the present findings suggest the importance of developing selective 5-HT1D alpha receptor agonists as a strategy to reduce the risk of myocardial infarction and possibly stroke that complicates the acute treatment of migraine headache.