Differences in pituitary adenylate cyclase-activating peptide and calcitonin gene-related peptide release in the trigeminovascular system.

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 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.

• Authors: Jacob Carl Alexander Edvinsson, Anne-Sofie Grell, Karin Warfvinge, Majid Sheykhzade, Lars Edvinsson, Kristian Agmund Haanes
• Journal: Cephalalgia : an international journal of headache (Cephalalgia) Vol. 40 Issue 12 Pg. 1296-1309 (10 2020) ISSN: 1468-2982 [Electronic] England
• PMID: 32486909 (Publication Type: Journal Article)

Chemical References

• Pituitary Adenylate Cyclase-Activating Polypeptide
• Calcitonin Gene-Related Peptide

Topics

• Animals
• Calcitonin Gene-Related Peptide (metabolism)
• Dura Mater (metabolism)
• Male
• Migraine Disorders (physiopathology)
• Pituitary Adenylate Cyclase-Activating Polypeptide (metabolism)
• Rats
• Rats, Sprague-Dawley
• Trigeminal Ganglion (metabolism)