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Selective inhibition of 5-HT7 receptor reduces CGRP release in an experimental model for migraine.
Headache 2010; 50(4):579-87H

Abstract

OBJECTIVE

To investigate the role of 5-HT(7) receptors on the release of calcitonin gene-related peptide (CGRP) in an animal model of migraine.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Authors+Show Affiliations

Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20236348

Citation

Wang, Xiaojuan, et al. "Selective Inhibition of 5-HT7 Receptor Reduces CGRP Release in an Experimental Model for Migraine." Headache, vol. 50, no. 4, 2010, pp. 579-87.
Wang X, Fang Y, Liang J, et al. Selective inhibition of 5-HT7 receptor reduces CGRP release in an experimental model for migraine. Headache. 2010;50(4):579-87.
Wang, X., Fang, Y., Liang, J., Yin, Z., Miao, J., & Luo, N. (2010). Selective inhibition of 5-HT7 receptor reduces CGRP release in an experimental model for migraine. Headache, 50(4), pp. 579-87. doi:10.1111/j.1526-4610.2010.01632.x.
Wang X, et al. Selective Inhibition of 5-HT7 Receptor Reduces CGRP Release in an Experimental Model for Migraine. Headache. 2010;50(4):579-87. PubMed PMID: 20236348.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective inhibition of 5-HT7 receptor reduces CGRP release in an experimental model for migraine. AU - Wang,Xiaojuan, AU - Fang,Yannan, AU - Liang,Jianbo, AU - Yin,Zhao, AU - Miao,Jiayin, AU - Luo,Ning, Y1 - 2010/03/05/ PY - 2010/3/19/entrez PY - 2010/3/20/pubmed PY - 2010/8/19/medline SP - 579 EP - 87 JF - Headache JO - Headache VL - 50 IS - 4 N2 - OBJECTIVE: To investigate the role of 5-HT(7) receptors on the release of calcitonin gene-related peptide (CGRP) in an animal model of migraine. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 1526-4610 UR - https://www.unboundmedicine.com/medline/citation/20236348/Selective_inhibition_of_5_HT7_receptor_reduces_CGRP_release_in_an_experimental_model_for_migraine_ L2 - https://doi.org/10.1111/j.1526-4610.2010.01632.x DB - PRIME DP - Unbound Medicine ER -