Longmore J, Shaw D, Smith D, Hopkins R, McAllister G, Pickard J D, Sirinathsinghji D J, Butler A J, Hill R G
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Cephalalgia. 1997 Dec;17(8):833-42. doi: 10.1046/j.1468-2982.1997.1708833.x.
Sumatriptan, a 5HT1B/1D-receptor agonist, is clinically effective as an antimigraine agent. Its therapeutic action may result partly from vasoconstriction of excessively dilated cranial blood vessels (a 5HT1B-receptor mediated response). The antimigraine activity of sumatriptan may also result from inhibition of the release of vasoactive neuropeptides from trigeminal sensory fibres within the meninges. The identity of the 5HT1B/1D-receptor subtype mediating this effect is unknown. Using 5HT1D- and 5HT1B-receptor-specific antibodies we have demonstrated a differential distribution of these receptor subtypes within the human trigemino-cerebrovascular system. Only 5HT1B-receptor protein was detected on dural arteries. In contrast, only 5HT1D-receptor protein was detected on trigeminal sensory neurones including peripheral and central projections to dural blood vessels and to the medulla. Within the medulla 5HT1D-receptor protein was confined to discrete areas associated with the trigeminal sensory system. These findings have important implications for the design of new antimigraine drugs.
舒马曲坦是一种5HT1B/1D受体激动剂，作为一种抗偏头痛药物在临床上有效。其治疗作用可能部分源于过度扩张的颅内血管的血管收缩（一种5HT1B受体介导的反应）。舒马曲坦的抗偏头痛活性也可能源于抑制脑膜内三叉神经感觉纤维释放血管活性神经肽。介导这种作用的5HT1B/1D受体亚型的身份尚不清楚。使用5HT1D和5HT1B受体特异性抗体，我们已经证明了这些受体亚型在人类三叉神经脑血管系统中的差异分布。在硬脑膜动脉上仅检测到5HT1B受体蛋白。相反，在三叉神经感觉神经元上仅检测到5HT1D受体蛋白，包括向硬脑膜血管和延髓的外周和中枢投射。在延髓内，5HT1D受体蛋白局限于与三叉神经感觉系统相关的离散区域。这些发现对新型抗偏头痛药物的设计具有重要意义。
