Vascular Actions of Calcitonin Gene-Related Peptide and Adrenomedullin
Abstract
This review summarizes the receptor-mediated vascular activities of calcitonin gene-related peptide (CGRP) and the structurally related peptide adrenomedullin (AM). CGRP is a 37-amino acid neuropeptide, primarily released from sensory nerves, whilst AM is produced by stimulated vascular cells, and amylin is secreted from the pancreas. They share vasodilator activity, albeit to varying extents depending on species and tissue. In particular, CGRP has potent activity in the cerebral circulation, which is possibly relevant to the pathology of migraine, whilst vascular sources of AM contribute to dysfunction in cardiovascular disease. Both peptides exhibit potent activity in microvascular beds. All three peptides can act on a family of CGRP receptors that consist of calcitonin receptor-like receptor (CL) linked to one of three receptor activity-modifying proteins (RAMPs) that are essential for functional activity. The association of CL with RAMP1 produces a CGRP receptor, with RAMP2 an AM receptor and with RAMP3 a CGRP/AM receptor. Evidence for the selective activity of the first nonpeptide CGRP antagonist BIBN4096BS for the CGRP receptor is presented. The cardiovascular activity of these peptides in a range of species and in human clinical conditions is detailed, and potential therapeutic applications based on use of antagonists and gene targeting of agonists are discussed.
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Genetic deletion or blockade of CGRP receptors is detrimental to wound healing.
“Similarly, genetic deletion or blockade of CGRP receptors has been suggested to be detrimental to wound healing58–60.”
From Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis (2019) · cites this paper as [59]
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Calcitonin Gene-Related Peptide Antagonists as Treatments of Migraine and Other Primary Headaches
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de Prado, B. M., Hammond, D. L., & Russo, A. F. (2009) · Journal of Pain · doi:10.1016/j.jpain.2009.03.018 · Cited by 83 · see citing works
Yan, D., Liu, X., & Guo, S.-W. (2019) · Scientific Reports · doi:10.1038/s41598-019-39170-w · Cited by 82 · see citing works
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- Authors
- Brain, S. D., & Grant, A. D.
- Affiliations
- King's College London (GB)
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2004-07
- Volume
- 84
- Issue
- 3
- Pages
- 903-934
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2102917831
- Cited by
- 765
- References
- 414
- Citations by year
- 2026: 23 · 2025: 30 · 2024: 29 · 2023: 25 · 2022: 19 · 2021: 29 · 2020: 29 · 2019: 43 · 2018: 34 · 2017: 27 · 2016: 30 · 2015: 30 · 2014: 43 · 2013: 44 · 2012: 34
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Edge Hill University Research Information Repository (Edge Hill University) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council (S18959)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Psychiatry and Mental health › Migraine and Headache Studies
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Keywords
- calcitonin gene-related peptide, adrenomedullin, amylin, CGRP receptor, calcitonin receptor-like receptor, receptor activity-modifying proteins, RAMP1, RAMP2, RAMP3, vasodilation, cerebral circulation, migraine, microvascular bed, cardiovascular disease, BIBN4096BS, CGRP antagonists, gene targeting, neuropeptides
- MeSH terms
- Amino Acid Sequence, Animals, Blood Vessels, Cardiovascular Diseases, Humans, Inflammation, Microcirculation, Molecular Sequence Data, Peptides, Tissue Distribution, Vasodilation, Calcitonin Gene-Related Peptide, Receptors, Peptide, Receptors, Calcitonin Gene-Related Peptide, Adrenomedullin, Receptors, Adrenomedullin
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