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Exploration of puri...
Exploration of purinergic receptors as potential anti-migraine targets using established pre-clinical migraine models
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- Haanes, Kristian A. (författare)
- Copenhagen University Hospital,Erasmus University Medical Center
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- Labastida-Ramírez, Alejandro (författare)
- Erasmus University Medical Center
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- Blixt, Frank W. (författare)
- Lund University,Lunds universitet,Experimentell kärlforskning,Forskargrupper vid Lunds universitet,Experimental Vascular Research,Lund University Research Groups
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- Rubio-Beltrán, Eloisa (författare)
- Erasmus University Medical Center
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- Dirven, Clemens M. (författare)
- Erasmus University Medical Center
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- Danser, Alexander H.J. (författare)
- Erasmus University Medical Center
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- Edvinsson, Lars (författare)
- Lund University,Lunds universitet,Experimentell kärlforskning,Forskargrupper vid Lunds universitet,Experimental Vascular Research,Lund University Research Groups,Copenhagen University Hospital
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- MaassenVanDenBrink, Antoinette (författare)
- Erasmus University Medical Center
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(creator_code:org_t)
- 2019-05-19
- 2019
- Engelska.
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 39:11, s. 1421-1434
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: The current understanding of mechanisms behind migraine pain has been greatly enhanced with the recent therapies targeting calcitonin gene-related peptide and its receptor. The clinical efficacy of calcitonin gene-related peptide-blocking drugs indicates that, at least in a considerable proportion of patients, calcitonin gene-related peptide is a key molecule in migraine pain. There are several receptors and molecular pathways that can affect the release of and response to calcitonin gene-related peptide. One of these could be purinergic receptors that are involved in nociception, but these are greatly understudied with respect to migraine. Objective: We aimed to explore purinergic receptors as potential anti-migraine targets. Methods: We used the human middle meningeal artery as a proxy for the trigeminal system to screen for possible anti-migraine candidates. The human findings were followed by intravital microscopy and calcitonin gene-related peptide release measurements in rodents. Results: We show that the purinergic P2Y13 receptor fulfills all the features of a potential anti-migraine target. The P2Y13 receptor is expressed in both the human trigeminal ganglion and middle meningeal artery and activation of this receptor causes: a) middle meningeal artery contraction in vitro; b) reduced dural artery dilation following periarterial electrical stimulation in vivo and c) a reduction of CGRP release from both the dura and the trigeminal ganglion in situ. Furthermore, we show that P2X3 receptor activation of the trigeminal ganglion causes calcitonin gene-related peptide release and middle meningeal artery dilation. Conclusion: Both an agonist directed at the P2Y13 receptor and an antagonist of the P2X3 receptor seem to be viable potential anti-migraine therapies.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- CGRP release
- middle meningeal artery
- myograph
- Novel drug candidates
- P2X3 receptor
- P2Y13 receptor
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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