Calcitonin gene-related peptide as inflammatory mediator.
Sensory neuropeptides have been proposed to play a key role in the pathogenesis of a number of respiratory diseases such as asthma, chronic obstructive pulmonary disease or chronic cough. Next to prominent neuropeptides such as tachykinins or vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) has long been suggested to participate in airway physiology and pathophysiology. CGRP is a 37 amino-acid peptide which is expressed by nerve fibers projecting to the airways and by pulmonary neuroendocrine cells. The most prominent effects of CGRP in the airways are vasodilatation and in a few instances bronchoconstriction. A further pulmonary effect of CGRP is the induction of eosinophil migration and the stimulation of beta-integrin-mediated T cell adhesion to fibronectin at the site of inflammation. By contrast, CGRP inhibits macrophage secretion and the capacity of macrophages to activate T-cells, indicating a potential anti-inflammatory effect. Due to the complex pulmonary effects of CGRP with bronchoconstriction and vasodilatation and diverse immunomodulatory actions, potential anti-asthma drugs based on this peptide have not been established so far. However, targeting the effects of CGRP may be of value for future strategies in nerve modulation.
Springer
Jochen
J
Division of Allergy Research, Department of Pediatric Pneumology and Immunology, Charité Campus-Virchow, Humboldt-University Berlin, 13353 Berlin, Germany.
Geppetti
Pierangelo
P
Fischer
Axel
A
Groneberg
David A
DA
D000818:Animals; D001249:Asthma / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000031:analogs & derivatives / Q000235:genetics / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D012137:Respiratory System / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D018836:Inflammation Mediators; D015740:Calcitonin Gene-Related Peptide