Rebeck G W, Maynard K I, Hyman B T, Moskowitz M A
Neurology Service, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3666-9. doi: 10.1073/pnas.91.9.3666.
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.
药理学数据表明，舒马曲坦等抗偏头痛药物的作用可能由三叉神经血管神经末梢上类似5-HT1D的5-羟色胺受体介导。我们使用与5-HT1B/D家族（人类5-HT1Dα和5-HT1Dβ；大鼠5-HT1B）编码序列独特同源的寡核苷酸进行聚合酶链反应，寻找豚鼠和人类三叉神经节中编码5-HT1D受体亚型的mRNA种类表达的分子证据。在豚鼠三叉神经节的样本中观察到一条预测大小的单带；序列分析显示存在单一信息，分别与人5-HT1Dα和5-HT1Dβ受体DNA序列有85%和71%的同一性。对死后人类三叉神经节的类似分析显示存在5-HT1Dα受体信息，但不存在5-HT1Dβ受体信息。鉴于最近一份报告发现，仅编码5-HT1Dβ受体亚型的mRNA由中枢神经系统的血管平滑肌表达，目前的研究结果表明，开发选择性5-HT1Dα受体激动剂作为一种策略以降低心肌梗死风险以及可能降低使偏头痛急性治疗复杂化的中风风险具有重要意义。
