Bouchelet I, Cohen Z, Case B, Séguéla P, Hamel E
Neurobiology Unit, Montreal Neurological Institute, Québec, Canada.
Mol Pharmacol. 1996 Aug;50(2):219-23.
The efficacy of sumatriptan in migraine relief has been attributed to its interaction with 5-hydroxytryptamine1D (5-HT1D) receptors in cerebral blood vessels and/or on nerve endings of the trigeminovascular system in the dura mater. Using the high sensitivity of polymerase chain reaction (PCR) amplification, we investigated the expression of the sumatriptan-sensitive 5-HT receptors, namely, the 5-HT1D alpha, 5-HT1D beta, and 5-HT1F subtypes in human trigeminal ganglia (10 experiments) and cerebral blood vessels (seven experiments) obtained postmortem. Messages for the 5-HT1D alpha and 5-HT1D beta receptors were expressed in all except one of the 10 trigeminal ganglia studied. Expression of the 5-HT1F receptor was detected by gel electrophoresis of the PCR products in six ganglia and by Southern blot hybridization in two additional cases. In human brain vessels, message for the 5-HT1D beta receptor was present in all samples, whereas specific PCR products corresponding to the 5-HT1D alpha receptor could hardly be detected in only two preparations. PCR products indicative of the 5-HT1F receptor message were detected by gel electrophoresis in three brain vessel preparations and confirmed in the other four by Southern blot hybridization. Restriction mapping and sequence analysis of all PCR products identified the expected human 5-HT receptor DNA sequences. The data confirm that the 5-HT1D beta receptor is the dominant species in human cerebral blood vessels and further show that this receptor and the 5-HT1F are expressed in both neural and vascular tissues. In contrast, the data point to a preferential expression of 5-HT1D alpha receptors in neural versus vascular tissues and strongly reemphasize the need for selective 5-HT1D alpha agonists in the identification of the target tissue(s) for antimigraine drugs. Moreover, the data stress the importance to better understand the role of 5-HT1F receptors in cerebrovascular functions and dural inflammation and further raise interest regarding their possible involvement in migraine therapy.
舒马曲坦缓解偏头痛的疗效归因于其与脑血管以及/或者硬脑膜中三叉神经血管系统神经末梢上的5-羟色胺1D（5-HT1D）受体的相互作用。利用聚合酶链反应（PCR）扩增的高灵敏度，我们研究了对舒马曲坦敏感的5-HT受体，即5-HT1Dα、5-HT1Dβ和5-HT1F亚型在死后获取的人三叉神经节（10次实验）和脑血管（7次实验）中的表达情况。在所研究的10个三叉神经节中，除1个外，其余均表达5-HT1Dα和5-HT1Dβ受体的信息。通过PCR产物的凝胶电泳在6个神经节中检测到了5-HT1F受体的表达，另外2例通过Southern印迹杂交检测到。在人脑血管中，所有样本均存在5-HT1Dβ受体的信息，而仅在2份标本中几乎检测不到与5-HT1Dα受体对应的特异性PCR产物。通过凝胶电泳在3份脑血管标本中检测到了指示5-HT1F受体信息的PCR产物，另外4份通过Southern印迹杂交得到证实。对所有PCR产物进行限制性酶切图谱分析和序列分析，确定了预期的人5-HT受体DNA序列。数据证实5-HT1Dβ受体是人类脑血管中的主要类型，进一步表明该受体和5-HT1F受体在神经组织和血管组织中均有表达。相比之下，数据表明5-HT1Dα受体在神经组织与血管组织中存在优先表达，强烈再次强调了在确定抗偏头痛药物的靶组织时需要选择性5-HT1Dα激动剂。此外，数据强调了更好地理解5-HT1F受体在脑血管功能和硬脑膜炎症中的作用的重要性，并进一步引发了对其可能参与偏头痛治疗的兴趣。
