Dual action of the cannabinoid receptor 1 ligand arachidonyl-2'-chloroethylamide on calcitonin gene-related peptide release.
ACEA
CGRP
Cannabinoid receptors
Immunohistochemistry
Trigeminal ganglion
Journal
The journal of headache and pain
ISSN: 1129-2377
Titre abrégé: J Headache Pain
Pays: England
ID NLM: 100940562
Informations de publication
Date de publication:
21 Feb 2022
21 Feb 2022
Historique:
received:
14
12
2021
accepted:
04
02
2022
entrez:
22
2
2022
pubmed:
23
2
2022
medline:
24
2
2022
Statut:
epublish
Résumé
Based on the current understanding of the role of neuropeptide signalling in migraine, we explored the therapeutic potential of a specific cannabinoid agonist. The aim of the present study was to examine the effect of the synthetic endocannabinoid (eCB) analogue, arachidonyl-2'-chloroethylamide (ACEA), on calcitonin gene-related peptide (CGRP) release in the dura and trigeminal ganglion (TG), as cannabinoids are known to activate G The experiments were performed using the hemi-skull model and dissected TGs from male Sprague-Dawley rats. CGRP release was induced by either 60 mM K CB1 was predominantly expressed in neuronal somas in which colocalization with CGRP was observed. Furthermore, CB1 exhibited colocalization with RAMP1 in neuronal Aδ-fibres but was not clearly expressed in the CGRP-immunoreactive C-fibres. CB2 was mainly expressed in satellite glial cells and did not show substantial colocalization with either CGRP or RAMP1. Without stimulation, 140 nM ACEA per se caused a significant increase in CGRP release in the dura but not TG, compared to vehicle. Furthermore, 140 nM ACEA did not significantly modify neither K Results from the present study indicate that ACEA per se does not exhibit antimigraine potential due to its dual agonistic properties, resulting in activation of both CB1 and TRPV1, and thereby inhibition and stimulation of CGRP release, respectively.
Sections du résumé
BACKGROUND
BACKGROUND
Based on the current understanding of the role of neuropeptide signalling in migraine, we explored the therapeutic potential of a specific cannabinoid agonist. The aim of the present study was to examine the effect of the synthetic endocannabinoid (eCB) analogue, arachidonyl-2'-chloroethylamide (ACEA), on calcitonin gene-related peptide (CGRP) release in the dura and trigeminal ganglion (TG), as cannabinoids are known to activate G
METHODS
METHODS
The experiments were performed using the hemi-skull model and dissected TGs from male Sprague-Dawley rats. CGRP release was induced by either 60 mM K
RESULTS
RESULTS
CB1 was predominantly expressed in neuronal somas in which colocalization with CGRP was observed. Furthermore, CB1 exhibited colocalization with RAMP1 in neuronal Aδ-fibres but was not clearly expressed in the CGRP-immunoreactive C-fibres. CB2 was mainly expressed in satellite glial cells and did not show substantial colocalization with either CGRP or RAMP1. Without stimulation, 140 nM ACEA per se caused a significant increase in CGRP release in the dura but not TG, compared to vehicle. Furthermore, 140 nM ACEA did not significantly modify neither K
CONCLUSIONS
CONCLUSIONS
Results from the present study indicate that ACEA per se does not exhibit antimigraine potential due to its dual agonistic properties, resulting in activation of both CB1 and TRPV1, and thereby inhibition and stimulation of CGRP release, respectively.
Identifiants
pubmed: 35189809
doi: 10.1186/s10194-022-01399-8
pii: 10.1186/s10194-022-01399-8
pmc: PMC8903492
doi:
Substances chimiques
Arachidonic Acids
0
Ligands
0
Receptors, Cannabinoid
0
arachidonyl-2-chloroethylamide
0
Calcitonin Gene-Related Peptide
JHB2QIZ69Z
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
30Subventions
Organisme : Lundbeckfonden
ID : R345-2020-1977
Informations de copyright
© 2022. The Author(s).
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