5-羟色胺1F受体激动剂可抑制豚鼠的神经源性硬脑膜炎症。

5-HT1F receptor agonists inhibit neurogenic dural inflammation in guinea pigs.

作者信息

Johnson K W, Schaus J M, Durkin M M, Audia J E, Kaldor S W, Flaugh M E, Adham N, Zgombick J M, Cohen M L, Branchek T A, Phebus L A

机构信息

Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46285, USA.

出版信息

Neuroreport. 1997 Jul 7;8(9-10):2237-40. doi: 10.1097/00001756-199707070-00029.

DOI:10.1097/00001756-199707070-00029

PMID:9243618

Abstract

The serotonin (5-HT) receptor subtype mediating inhibition of neurogenic dural inflammation in guinea pigs was investigated using a series of serotonin agonists with differing affinities for the 5-HT1B, 5-HT1D and 5-HT1F receptors. When agonist potencies for inhibiting neurogenic inflammation were compared with affinities for these receptor subtypes, a significant positive correlation was seen only with the 5-HT1F receptor. The potency of agonists in inhibiting adenylate cyclase in cells transfected with human 5-HT1F receptor was also highly correlated with their potency in the animal model of migraine. In situ hybridization demonstrated 5-HT1F receptor mRNA in guinea pig trigeminal ganglion neurons. These data suggest that the 5-HT1F receptor is a rational target for migraine therapeutics.

摘要

利用一系列对5-HT1B、5-HT1D和5-HT1F受体具有不同亲和力的5-羟色胺（5-HT）激动剂，研究了介导豚鼠神经源性硬脑膜炎症抑制作用的5-羟色胺受体亚型。当将抑制神经源性炎症的激动剂效力与这些受体亚型的亲和力进行比较时，仅在5-HT1F受体上观察到显著的正相关。激动剂在转染人5-HT1F受体的细胞中抑制腺苷酸环化酶的效力也与其在偏头痛动物模型中的效力高度相关。原位杂交显示豚鼠三叉神经节神经元中有5-HT1F受体mRNA。这些数据表明5-HT1F受体是偏头痛治疗的合理靶点。