Effects of alpha calcitonin gene-related peptide in human bronchial smooth muscle and pulmonary artery

Springer, Jochen, Amadesi, Silvia, Trevisani, Marcello, Harrison, Selena, Din, Q. Thai, McGregor, Gerald P., Fischer, Axel, Fischer, Pierangelo and Groneberg, David A (2004) Effects of alpha calcitonin gene-related peptide in human bronchial smooth muscle and pulmonary artery. Regulatory Peptides, 118 (3). pp. 127-134. ISSN 1873-1686

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Although airway and pulmonary vessel tone are regulated predominantly by cholinergic and adrenergic impulses, biologically active peptides such as calcitonin gene-related peptide (CGRP) may significantly influence human smooth muscle tone in normal and pathophysiological states. In the present study, the expression of CGRP and its receptor CGRPR-1 and the biological effect of the peptide were investigated in human airways and pulmonary arteries. Immunohistochemistry revealed the presence of CGRP in human airway nerves and neuro-epithelial cells, whereas the receptor was found in epithelial cells and smooth muscle myocytes of the bronchi and in pulmonary artery endothelium. On precontracted bronchi (3–4 mm in diameter) alpha-CGRP (0.01–10 nM) caused a concentration-dependent contraction on epithelium-denuded bronchi, whereas no significant effect was recorded in bronchi with intact epithelium. In pulmonary arteries (2–6 mm in diameter), alpha-CGRP caused a concentration-dependent relaxation of endothelium intact and denuded vessels. Pre-treatment with indomethacin, but not with l-NAME, prevented the relaxation induced by alpha-CGRP in pulmonary arteries suggesting that prostaglandins but not nitric oxide (NO) are involved in the intracellular signal transduction pathway. The effects induced by alpha-CGRP in bronchi and vessels were prevented by application of the antagonist CGRP(8–37). In summary, the present studies examined the biological function of CGRP in human airways and demonstrated a constrictory effect of CGRP only in epithelium-denuded airway smooth muscle indicating an alteration of CGRP airway effects in respiratory tract pathological states with damaged epithelium such as chronic obstructive pulmonary disease or bronchial asthma.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User: Rhiannon Harvey
Date Deposited: 08 Jun 2011 15:46
Last Modified: 07 Mar 2023 09:29
URI: https://ueaeprints.uea.ac.uk/id/eprint/32079
DOI: 10.1016/j.regpep.2003.11.006

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