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The CGRP Family of Neuropeptides and their Receptors in the Trigeminovascular System

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Monoclonal Antibodies in Headache

Part of the book series: Headache ((HEAD))

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Abstract

The calcitonin gene-related peptide (CGRP) family of peptides includes CGRP itself, calcitonin (CT), adrenomedullin (AM), and amylin (AMY). The peptides share several aspects of G-protein-coupled receptors. The 7-transmembrane (7TM) part of the receptor has either the calcitonin receptor like-receptor (CLR) or the calcitonin receptor (CTR) which for function needs an accessory protein, receptor activity-modifying proteins (RAMPs) 1, 2, or 3. The RAMPs interact to produce different effects via signal transduction and receptor trafficking. Current research has shown that CGRP has a pivotal role in primary headaches while the role of the other peptides or receptors is unclear. The purpose of this paper is to describe their expression in the trigeminal system and to discuss their putative role in migraine.

We observed the peptides CGRP and CT in small- to medium-sized neurons in the trigeminal ganglion (TG), forming immunoreactive C-fibers originating from these neurons. Adrenomedullin was observed in satellite glial cells and fibers, probably processes of the myelinating glial cells in the TG. Amylin was found in the cytoplasm of several TG neurons.

The CGRP receptor (CLR/RAMP1) and the CTR, without a RAMP, were found in the TG, mainly in larger neurons probably forming Aδ-fibers. Furthermore, we observed adrenomedullin receptor AM2 (CLR/RAMP3) mainly in SGCs, the amylin receptor AMY1 (CTR/RAMP1) in neurons, and the AMY3 receptor (CTR/RAMP3) in SGCs.

The wide spectrum of the CGRP family of peptides and receptors in the trigeminal system suggests a role but it is still unclear how this relates to the function of the trigeminovascular system and involvement in the sensory function of the head.

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Authors and Affiliations

  1. Department of Internal Medicine, Lund University Hospital, Lund, Sweden

    Lars Edvinsson & Karin Warfvinge

  2. Department of Clinical Experimental Research, Glostrup Research Institute, Glostrup Hospital, Rigshospitalet, Glostrup, Denmark

    Lars Edvinsson & Karin Warfvinge

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  1. Lars Edvinsson
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Correspondence to Lars Edvinsson .

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Editors and Affiliations

  1. Internal Medicine, Erasmus University Medical Center, Rotterdam, Zuid-Holland, The Netherlands

    Antoinette Maassen van den Brink

  2. Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy

    Paolo Martelletti

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Edvinsson, L., Warfvinge, K. (2021). The CGRP Family of Neuropeptides and their Receptors in the Trigeminovascular System. In: Maassen van den Brink, A., Martelletti, P. (eds) Monoclonal Antibodies in Headache . Headache. Springer, Cham. https://doi.org/10.1007/978-3-030-69032-8_1

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  • DOI: https://doi.org/10.1007/978-3-030-69032-8_1

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