Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide. Discovered 30 years ago, it is produced as a consequence of alternative RNA processing of the calcitonin gene. CGRP has two major forms (α and β). It belongs to a group of peptides that all act on an unusual receptor family. These receptors consist of calcitonin receptor-like receptor (CLR) linked to an essential receptor activity modifying protein (RAMP) that is necessary for full functionality. CGRP is a highly potent vasodilator and, partly as a consequence, possesses protective mechanisms that are important for physiological and pathological conditions involving the cardiovascular system and wound healing. CGRP is primarily released from sensory nerves and thus is implicated in pain pathways. The proven ability of CGRP antagonists to alleviate migraine has been of most interest in terms of drug development, and knowledge to date concerning this potential therapeutic area is discussed. Other areas covered, where there is less information known on CGRP, include arthritis, skin conditions, diabetes, and obesity. It is concluded that CGRP is an important peptide in mammalian biology, but it is too early at present to know if new medicines for disease treatment will emerge from our knowledge concerning this molecule.

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Calcitonin gene-related peptide (CGRP) is a potent microvascular vasodilator derived predominantly from perivascular sensory neurones. It has been suggested that vascular reactivity to CGRP is diminished with increasing age whilst levels of CGRP are also thought to decline. Our aim was to investigate how vascular responses to CGRP changed with age in α-CGRP wild type (WT) and knockout (KO) mice. Male and female α-CGRP WT and KO mice were aged to 15 months at which point mice were killed and second order mesenteric arteries were mounted in a wire myograph. Aortic tissue was collected and mRNA expression of CGRP receptor subunits was evaluated by RTqPCR. Data were analysed by ANOVA and Student's t test, where appropriate.Maximal relaxation to CGRP (100 nM) in aged WT mice produced a 75.30±7.48% relaxation from initial tone induced by 10 nM U46619. Conversely, maximal relaxation to CGRP in aged KO vessels produced a 31.33±8.74% decline in tone, an effect found to be significantly different ( p<0.01). Analysis of gene expression of CGRP receptor subunits (calcitonin receptor-like receptor, receptor activity modifying protein 1 and receptor component protein) found a general trend towards an increase in expression within the aortic wall. This study has shown that whilst vascular reactivity to CGRP is diminished with advancing age, it does not appear to be as a result of decreased receptor expression.This project is funded by The British Heart Foundation.