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

Regul Pept. 2004 May 15;118(3):127-34. doi: 10.1016/j.regpep.2003.11.006.


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.

MeSH terms

  • Acetylcholine / pharmacology
  • Bronchi / chemistry
  • Bronchi / drug effects
  • Bronchi / physiology*
  • Calcitonin Gene-Related Peptide / analysis
  • Calcitonin Gene-Related Peptide / pharmacology
  • Calcitonin Gene-Related Peptide / physiology*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / chemistry
  • Endothelium, Vascular / physiology
  • Epithelium / chemistry
  • Epithelium / physiology
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Indomethacin / pharmacology
  • Muscle Contraction / drug effects
  • Muscle Relaxation / drug effects
  • Muscle, Smooth / chemistry
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Myocytes, Smooth Muscle / chemistry
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nerve Fibers / chemistry
  • Peptide Fragments / pharmacology
  • Phenylephrine / pharmacology
  • Pulmonary Artery / chemistry
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / physiology*
  • Receptors, Calcitonin Gene-Related Peptide / analysis


  • Peptide Fragments
  • Receptors, Calcitonin Gene-Related Peptide
  • calcitonin gene-related peptide (8-37)
  • Phenylephrine
  • Calcitonin Gene-Related Peptide
  • Acetylcholine
  • NG-Nitroarginine Methyl Ester
  • Indomethacin