The Effect of KATP Channel Blocker Glibenclamide on CGRP-Induced Headache and Hemodynamic in Healthy Volunteers
BackgroundCalcitonin gene-related peptide (CGRP) dilates cranial arteries and triggers headache. The CGRP signaling pathway is partly dependent on activation of ATP-sensitive potassium (KATP) channels. Here, we investigated the effect of the KATP channel blocker glibenclamide on CGRP-induced headach...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.652136/full |
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| author | Hande Coskun Fatima Azzahra Elbahi Fatima Azzahra Elbahi Mohammad Al-Mahdi Al-Karagholi Hashmat Ghanizada Majid Sheykhzade Messoud Ashina Messoud Ashina |
| author_facet | Hande Coskun Fatima Azzahra Elbahi Fatima Azzahra Elbahi Mohammad Al-Mahdi Al-Karagholi Hashmat Ghanizada Majid Sheykhzade Messoud Ashina Messoud Ashina |
| author_sort | Hande Coskun |
| collection | DOAJ |
| description | BackgroundCalcitonin gene-related peptide (CGRP) dilates cranial arteries and triggers headache. The CGRP signaling pathway is partly dependent on activation of ATP-sensitive potassium (KATP) channels. Here, we investigated the effect of the KATP channel blocker glibenclamide on CGRP-induced headache and vascular changes in healthy volunteers.MethodsIn a randomized, double-blind, placebo-controlled, cross-over study, 20 healthy volunteers aged 18–27 years were randomly allocated to receive an intravenous infusion of 1.5 μg/min CGRP after oral pretreatment with glibenclamide (glibenclamide-CGRP day) or placebo (placebo-CGRP day). The primary endpoints were the difference in incidence of headache and the difference in area under the curve (AUC) for headache intensity scores (0–14 h) between glibenclamide and placebo. The secondary endpoints were the difference in AUC for middle cerebral artery blood flow velocity (VMCA), superficial temporal artery (STA) and radial artery (RA) diameter, facial flushing, heart rate (HR) and mean arterial blood pressure (MAP) (0–4 h) between glibenclamide and placebo.ResultsWe found no significant difference in the incidence of headache between glibenclamide-CGRP day (14/20, 70%) and placebo-CGRP day (19/20, 95%) (P = 0.06). The AUC for headache intensity, VMCA, STA, RA, facial skin blood flow, HR, and MAP did not differ between glibenclamide-CGRP day compared to placebo-CGRP day (P > 0.05).ConclusionPretreatment with a non-selective KATP channel inhibitor glibenclamide did not attenuate CGRP-induced headache and hemodynamic changes in healthy volunteers. We suggest that CGRP-induced responses could be mediated via activation of specific isoforms of sulfonylurea receptor subunits of KATP channel. |
| first_indexed | 2024-12-17T18:01:52Z |
| format | Article |
| id | doaj.art-ad476ca140d44eaf8cc8efa7acf4ac92 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-17T18:01:52Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Physiology |
| spelling | doaj.art-ad476ca140d44eaf8cc8efa7acf4ac922022-12-21T21:38:18ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-06-011210.3389/fphys.2021.652136652136The Effect of KATP Channel Blocker Glibenclamide on CGRP-Induced Headache and Hemodynamic in Healthy VolunteersHande Coskun0Fatima Azzahra Elbahi1Fatima Azzahra Elbahi2Mohammad Al-Mahdi Al-Karagholi3Hashmat Ghanizada4Majid Sheykhzade5Messoud Ashina6Messoud Ashina7Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDanish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDanish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDanish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDanish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDanish Headache Knowledge Center, Rigshospitalet Glostrup, Glostrup, DenmarkBackgroundCalcitonin gene-related peptide (CGRP) dilates cranial arteries and triggers headache. The CGRP signaling pathway is partly dependent on activation of ATP-sensitive potassium (KATP) channels. Here, we investigated the effect of the KATP channel blocker glibenclamide on CGRP-induced headache and vascular changes in healthy volunteers.MethodsIn a randomized, double-blind, placebo-controlled, cross-over study, 20 healthy volunteers aged 18–27 years were randomly allocated to receive an intravenous infusion of 1.5 μg/min CGRP after oral pretreatment with glibenclamide (glibenclamide-CGRP day) or placebo (placebo-CGRP day). The primary endpoints were the difference in incidence of headache and the difference in area under the curve (AUC) for headache intensity scores (0–14 h) between glibenclamide and placebo. The secondary endpoints were the difference in AUC for middle cerebral artery blood flow velocity (VMCA), superficial temporal artery (STA) and radial artery (RA) diameter, facial flushing, heart rate (HR) and mean arterial blood pressure (MAP) (0–4 h) between glibenclamide and placebo.ResultsWe found no significant difference in the incidence of headache between glibenclamide-CGRP day (14/20, 70%) and placebo-CGRP day (19/20, 95%) (P = 0.06). The AUC for headache intensity, VMCA, STA, RA, facial skin blood flow, HR, and MAP did not differ between glibenclamide-CGRP day compared to placebo-CGRP day (P > 0.05).ConclusionPretreatment with a non-selective KATP channel inhibitor glibenclamide did not attenuate CGRP-induced headache and hemodynamic changes in healthy volunteers. We suggest that CGRP-induced responses could be mediated via activation of specific isoforms of sulfonylurea receptor subunits of KATP channel.https://www.frontiersin.org/articles/10.3389/fphys.2021.652136/fullhumansmigraineglyburidecalcitonin-gene related peptidecranial arteries |
| spellingShingle | Hande Coskun Fatima Azzahra Elbahi Fatima Azzahra Elbahi Mohammad Al-Mahdi Al-Karagholi Hashmat Ghanizada Majid Sheykhzade Messoud Ashina Messoud Ashina The Effect of KATP Channel Blocker Glibenclamide on CGRP-Induced Headache and Hemodynamic in Healthy Volunteers Frontiers in Physiology humans migraine glyburide calcitonin-gene related peptide cranial arteries |
| title | The Effect of KATP Channel Blocker Glibenclamide on CGRP-Induced Headache and Hemodynamic in Healthy Volunteers |
| title_full | The Effect of KATP Channel Blocker Glibenclamide on CGRP-Induced Headache and Hemodynamic in Healthy Volunteers |
| title_fullStr | The Effect of KATP Channel Blocker Glibenclamide on CGRP-Induced Headache and Hemodynamic in Healthy Volunteers |
| title_full_unstemmed | The Effect of KATP Channel Blocker Glibenclamide on CGRP-Induced Headache and Hemodynamic in Healthy Volunteers |
| title_short | The Effect of KATP Channel Blocker Glibenclamide on CGRP-Induced Headache and Hemodynamic in Healthy Volunteers |
| title_sort | effect of katp channel blocker glibenclamide on cgrp induced headache and hemodynamic in healthy volunteers |
| topic | humans migraine glyburide calcitonin-gene related peptide cranial arteries |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.652136/full |
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