Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Headache. 2010 Apr;50(4):579-87. doi: 10.1111/j.1526-4610.2010.01632.x. Epub 2010 Mar 5.
To investigate the role of 5-HT(7) receptors on the release of calcitonin gene-related peptide (CGRP) in an animal model of migraine.
Calcitonin gene-related peptide has been identified as a key neuropeptide in the pathophysiology of migraine. It is elevated in the external jugular vein during migraine attacks in humans and after stimulation of the trigeminal ganglion in animal models of migraine. This can be treated with the 5-HT(1B/1D) receptor agonist sumatriptan concomitant with headache relief. Nevertheless, triptans, the most effective agents for the treatment of acute migraine attacks, are not effective in more than 1/3 of migraineurs and less than 50% of migraineurs achieve complete pain freedom. This indicates other serotonin receptors may be involved in the pathophysiology of migraine. Increasing evidence has shown that 5-HT(7) receptors may be involved in migraine pathogenesis. However, direct evidence for the role of 5-HT(7) receptors in migraine is still lacking.
Unilateral electrical stimulation of the trigeminal ganglion (TGES) was performed in anesthetized male Sprague-Dawley rats. Animals were pretreated with sumatriptan (300 microg/kg, i.v.), selective 5-HT(7) receptor antagonist SB269970 (5, 10 mg/kg, s.c.), potential 5-HT(7) receptor agonist AS19 (5, 10 mg/kg, s.c.) or co-administration of SB269970 and AS19 (10 mg/kg, s.c.). Serum CGRP concentrations in the ipsilateral jugular vein were determined before and at 2 and 5 minutes after the start of TGES.
Our results showed that sumatriptan almost completely inhibited the release of CGRP evoked by TGES. Pre-administration of SB269970 (5, 10 mg/kg) caused a significant decrease in serum CGRP concentrations at 2 and 5 minutes following the onset of TGES, with a less inhibitory effect compared with sumatriptan. AS19 had no significant effect on CGRP release, while the SB269970-induced inhibitory effect was reversed by AS19.
Selective inhibition of 5-HT(7) receptors partly reduced CGRP release evoked by TGES. These findings suggest that 5-HT(7) receptors may play a role in the pathophysiology of migraine.
探讨 5-HT（7）受体在偏头痛动物模型中降钙素基因相关肽（CGRP）释放中的作用。
降钙素基因相关肽已被确定为偏头痛病理生理学中的关键神经肽。在人类偏头痛发作期间和偏头痛动物模型的三叉神经节刺激后，其在外颈静脉中升高。这可以用 5-HT（1B/1D）受体激动剂舒马曲坦治疗，同时缓解头痛。然而，曲坦类药物是治疗急性偏头痛发作最有效的药物，但超过 1/3 的偏头痛患者无效，不到 50%的偏头痛患者完全缓解疼痛。这表明其他 5-羟色胺受体可能参与偏头痛的病理生理学。越来越多的证据表明，5-HT（7）受体可能与偏头痛的发病机制有关。然而，5-HT（7）受体在偏头痛中的作用仍缺乏直接证据。
在麻醉雄性 Sprague-Dawley 大鼠中进行单侧三叉神经节电刺激（TGES）。动物先用舒马曲坦（300μg/kg，iv）、选择性 5-HT（7）受体拮抗剂 SB269970（5、10mg/kg，sc）、潜在 5-HT（7）受体激动剂 AS19（5、10mg/kg，sc）预处理，或同时给予 SB269970 和 AS19（10mg/kg，sc）。在 TGES 开始前和开始后 2 分钟和 5 分钟，测定同侧颈静脉血清 CGRP 浓度。
我们的结果表明，舒马曲坦几乎完全抑制了 TGES 诱发的 CGRP 释放。SB269970（5、10mg/kg）预处理可显著降低 TGES 后 2 分钟和 5 分钟血清 CGRP 浓度，抑制作用弱于舒马曲坦。AS19 对 CGRP 释放无明显影响，而 SB269970 诱导的抑制作用可被 AS19 逆转。
选择性抑制 5-HT（7）受体可部分减少 TGES 诱发的 CGRP 释放。这些发现表明 5-HT（7）受体可能在偏头痛的病理生理学中发挥作用。
