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Exploration of purinergic receptors as potential anti-migraine targets using established pre-clinical migraine models.
Cephalalgia 2019; 39(11):1421-1434C

Abstract

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.

Authors+Show Affiliations

Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. Clinical Experimental Research Department, Copenhagen University Hospital, Rigshospitalet-Glostrup, Glostrup, Denmark.Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.Department of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Lund, Sweden.Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands.Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.Clinical Experimental Research Department, Copenhagen University Hospital, Rigshospitalet-Glostrup, Glostrup, Denmark. Department of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Lund, Sweden.Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31104506

Citation

Haanes, Kristian A., et al. "Exploration of Purinergic Receptors as Potential Anti-migraine Targets Using Established Pre-clinical Migraine Models." Cephalalgia : an International Journal of Headache, vol. 39, no. 11, 2019, pp. 1421-1434.
Haanes KA, Labastida-Ramírez A, Blixt FW, et al. Exploration of purinergic receptors as potential anti-migraine targets using established pre-clinical migraine models. Cephalalgia. 2019;39(11):1421-1434.
Haanes, K. A., Labastida-Ramírez, A., Blixt, F. W., Rubio-Beltrán, E., Dirven, C. M., Danser, A. H., ... MaassenVanDenBrink, A. (2019). Exploration of purinergic receptors as potential anti-migraine targets using established pre-clinical migraine models. Cephalalgia : an International Journal of Headache, 39(11), pp. 1421-1434. doi:10.1177/0333102419851810.
Haanes KA, et al. Exploration of Purinergic Receptors as Potential Anti-migraine Targets Using Established Pre-clinical Migraine Models. Cephalalgia. 2019;39(11):1421-1434. PubMed PMID: 31104506.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exploration of purinergic receptors as potential anti-migraine targets using established pre-clinical migraine models. AU - Haanes,Kristian A, AU - Labastida-Ramírez,Alejandro, AU - Blixt,Frank W, AU - Rubio-Beltrán,Eloisa, AU - Dirven,Clemens M, AU - Danser,Alexander Hj, AU - Edvinsson,Lars, AU - MaassenVanDenBrink,Antoinette, Y1 - 2019/05/19/ PY - 2019/5/21/pubmed PY - 2019/5/21/medline PY - 2019/5/21/entrez KW - CGRP release KW - Novel drug candidates KW - P2X3 receptor KW - P2Y13 receptor KW - middle meningeal artery KW - myograph SP - 1421 EP - 1434 JF - Cephalalgia : an international journal of headache JO - Cephalalgia VL - 39 IS - 11 N2 - 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. SN - 1468-2982 UR - https://www.unboundmedicine.com/medline/citation/31104506/Exploration_of_purinergic_receptors_as_potential_anti-migraine_targets_using_established_pre-clinical_migraine_models L2 - http://journals.sagepub.com/doi/full/10.1177/0333102419851810?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -