Differences in pituitary adenylate cyclase-activating peptide and calcitonin gene-related peptide release in the trigeminovascular system
(2020) In Cephalalgia 40(12). p.1296-1309- Abstract
Background: Several neurotransmitters are expressed in the neurons of the trigeminal ganglion. One such signalling molecule is the pituitary adenylate cyclase-activating peptide (PACAP). PACAP signalling has been suggested to have a possible role in the pathophysiology of primary headaches. Objective: The present study was designed to investigate the relationship between PACAP and calcitonin gene-related peptide, currently the two most relevant migraine peptides. Methods: In the current study, we used ELISA to investigate PACAP and calcitonin gene-related peptide release in response to 60 mM K+ or capsaicin using a rat hemi-skull model. We combined this analysis with qPCR and immunohistochemistry to study the expression of... (More)
Background: Several neurotransmitters are expressed in the neurons of the trigeminal ganglion. One such signalling molecule is the pituitary adenylate cyclase-activating peptide (PACAP). PACAP signalling has been suggested to have a possible role in the pathophysiology of primary headaches. Objective: The present study was designed to investigate the relationship between PACAP and calcitonin gene-related peptide, currently the two most relevant migraine peptides. Methods: In the current study, we used ELISA to investigate PACAP and calcitonin gene-related peptide release in response to 60 mM K+ or capsaicin using a rat hemi-skull model. We combined this analysis with qPCR and immunohistochemistry to study the expression of PACAP and calcitonin gene-related peptide receptors and ligands. Results: Calcitonin gene-related peptide (CGRP) is released from the trigeminal ganglion and dura mater. In contrast, PACAP is only released from the trigeminal ganglion. We observed a weak correlation between the stimulated release of the two neuropeptides. PACAP-38 immunoreactivity was expressed alone and in a subpopulation of neurons in the trigeminal ganglion that also store calcitonin gene-related peptide. The receptor subtype PAC1 was mainly expressed in the satellite glial cells (SGCs), which envelop the neurons in the trigeminal ganglion, in some neuronal processes, inside the Aδ-fibres and in the outermost layer of the myelin sheath that envelopes the Aδ-fibres. Conclusion: Unlike CGRP, PACAP is only released within the trigeminal ganglion. This raises the question of whether a migraine therapy aimed at preventing peripheral PACAP signalling would be as successful as the CGRP signalling targeted treatments.
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- author
- Edvinsson, Jacob Carl Alexander LU ; Grell, Anne Sofie LU ; Warfvinge, Karin LU ; Sheykhzade, Majid ; Edvinsson, Lars LU and Haanes, Kristian Agmund
- organization
- publishing date
- 2020-10-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- CGRP, hemi-skull model, PAC1 receptor, PACAP, Sensory nervous system, trigeminal ganglion
- in
- Cephalalgia
- volume
- 40
- issue
- 12
- pages
- 14 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:85086019921
- pmid:32486909
- ISSN
- 0333-1024
- DOI
- 10.1177/0333102420929026
- language
- English
- LU publication?
- yes
- id
- 895def9a-e910-4bde-890c-3fb94cf373ee
- date added to LUP
- 2020-07-03 11:19:23
- date last changed
- 2024-09-20 01:02:40
@article{895def9a-e910-4bde-890c-3fb94cf373ee, abstract = {{<p>Background: Several neurotransmitters are expressed in the neurons of the trigeminal ganglion. One such signalling molecule is the pituitary adenylate cyclase-activating peptide (PACAP). PACAP signalling has been suggested to have a possible role in the pathophysiology of primary headaches. Objective: The present study was designed to investigate the relationship between PACAP and calcitonin gene-related peptide, currently the two most relevant migraine peptides. Methods: In the current study, we used ELISA to investigate PACAP and calcitonin gene-related peptide release in response to 60 mM K<sup>+</sup> or capsaicin using a rat hemi-skull model. We combined this analysis with qPCR and immunohistochemistry to study the expression of PACAP and calcitonin gene-related peptide receptors and ligands. Results: Calcitonin gene-related peptide (CGRP) is released from the trigeminal ganglion and dura mater. In contrast, PACAP is only released from the trigeminal ganglion. We observed a weak correlation between the stimulated release of the two neuropeptides. PACAP-38 immunoreactivity was expressed alone and in a subpopulation of neurons in the trigeminal ganglion that also store calcitonin gene-related peptide. The receptor subtype PAC<sub>1</sub> was mainly expressed in the satellite glial cells (SGCs), which envelop the neurons in the trigeminal ganglion, in some neuronal processes, inside the Aδ-fibres and in the outermost layer of the myelin sheath that envelopes the Aδ-fibres. Conclusion: Unlike CGRP, PACAP is only released within the trigeminal ganglion. This raises the question of whether a migraine therapy aimed at preventing peripheral PACAP signalling would be as successful as the CGRP signalling targeted treatments.</p>}}, author = {{Edvinsson, Jacob Carl Alexander and Grell, Anne Sofie and Warfvinge, Karin and Sheykhzade, Majid and Edvinsson, Lars and Haanes, Kristian Agmund}}, issn = {{0333-1024}}, keywords = {{CGRP; hemi-skull model; PAC1 receptor; PACAP; Sensory nervous system; trigeminal ganglion}}, language = {{eng}}, month = {{10}}, number = {{12}}, pages = {{1296--1309}}, publisher = {{Wiley-Blackwell}}, series = {{Cephalalgia}}, title = {{Differences in pituitary adenylate cyclase-activating peptide and calcitonin gene-related peptide release in the trigeminovascular system}}, url = {{http://dx.doi.org/10.1177/0333102420929026}}, doi = {{10.1177/0333102420929026}}, volume = {{40}}, year = {{2020}}, }