Cited by 768Neuropeptides and Animal PhysiologyMigraine and Headache StudiesCardiovascular, Neuropeptides, and Oxidative Stress Research

Vascular Actions of Calcitonin Gene-Related Peptide and Adrenomedullin

Brain, Susan D., Grant, Andrew D.·2004·Physiological Reviews

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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Crossref · 10.1152/physrev.00037.2003

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Authors
Brain, S. D., & Grant, A. D.
Affiliations
King's College London (GB)
Venue
Physiological Reviews
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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