5-HYDROXYTRYPTAMINE RECEPTOR AGONISTS FOR THE ABORTIVE TREATMENT OF VASCULAR HEADACHES BLOCK MAST-CELL, ENDOTHELIAL AND PLATELET ACTIVATION WITHIN THE RAT DURA-MATER AFTER TRIGEMINAL STIMULATION
5-HYDROXYTRYPTAMINE RECEPTOR AGONISTS FOR THE ABORTIVE TREATMENT OF VASCULAR HEADACHES BLOCK MAST-CELL, ENDOTHELIAL AND PLATELET ACTIVATION WITHIN THE RAT DURA-MATER AFTER TRIGEMINAL STIMULATION
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DOI：
10.1016/s0006-8993(10)80017-4
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发表时间：
1992-06-26
期刊：
影响因子：
2.9
通讯作者：
MOSKOWITZ, MA
中科院分区：
文献类型：
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作者：
BUZZI, MG;DIMITRIADOU, V;MOSKOWITZ, MA
逆行刺激小口径三叉神经轴突会在硬脑膜和舌部引起神经源性炎症，表现为肥大细胞激活、蛋白质外溢以及同侧毛细血管后小静脉内内皮细胞质小泡、内皮细胞微绒毛和血小板聚集体数量显著增加。在这篇报道中，我们研究了5-羟色胺-1受体激动剂二氢麦角胺(50-mU-g/kg，静脉注射)的预处理效果。和舒马曲坦(100-mU-g/kg，i.v)三叉神经节刺激后的光镜和电子显微镜观察。二氢麦角胺和舒马曲坦均可用于血管头痛的急性治疗，并与5-HT1D受体高度结合。两种药物均可显著减少出现内皮或血小板改变的硬脑膜血管数目和激活的肥大细胞数目，但不影响舌的神经源性反应。这些药物还阻止了辣根过氧化物酶反应产物在刺激侧血管内皮细胞和血管周围空间的积聚。该受体不存在于支配颅外头部组织的三叉神经血管纤维上。药物机制可能涉及抑制病理生理学级联反应的近端步骤(例如，通过激活连接前受体)，因为(A)肥大细胞上尚未发现舒马曲坦的受体，而肥大细胞以及血小板和内皮内的炎症反应被减弱，以及(B)先前的工作表明舒马曲坦和二氢麦角胺阻断神经递质的释放。因此，连接后5-羟色胺受体介导的血管平滑肌收缩不太可能解释二氢麦角胺或舒马曲普坦的抗炎作用。
Antidromic stimulation of small caliber trigeminal axons causes neurogenic inflammation in the dura mater and tongue as evidenced by marked increases in mast cell activation, protein extravasation, as well as in the numbers of endothelial cytoplasmic vesicles, endothelial microvilli and platelet aggregates within ipsilateral post-capillary venules. In this report, we examined the effects of pretreatment with serotonin1 receptor agonists, dihydroergotamine (50-mu-g/kg, i.v.) and sumatriptan (100-mu-g/kg, i.v.) on the light and electron microscopic changes which develop after trigeminal ganglion stimulation. Both dihydroergotamine and sumatriptan are useful in the acute treatment of vascular headaches and bind with high affinity to 5-HT1D receptors. Both drugs decreased significantly the number of dural vessels showing endothelial or platelet changes and the numbers of activated mast cells, but did not affect the neurogenic response in the tongue. The drugs also blocked the accumulation of horseradish peroxidase reaction product within the endothelium and perivascular space on the stimulated side. The receptor is not present on trigeminovascular fibers innervating extracranial cephalic tissues. Drug mechanism probably involves inhibition of a proximal step in the pathophysiological cascade (e.g., via activation of a prejunctional receptor) because (a) receptors for sumatriptan have not been identified on mast cells whereas the inflammatory response was attenuated in mast cells as well as within platelets and the endothelium and (b) previous work indicates that sumatriptan and dihydroergotamine block neurotransmitter release. Hence, constriction of vascular smooth muscle mediated by postjunctional 5-hydroxytryptamine receptors is unlikely to explain the anti-inflammatory actions of dihydroergotamine or sumatriptan reported here.