Effects of alpha calcitonin gene-related peptide in human bronchial smooth muscle and pulmonary artery.
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.
Departments of Pediatric Pneumology, Biomedical Research Center, Charité School of Medicine, Humboldt-University, Augustenburger Platz 1 OR-1, D-13353 Berlin, Germany.
Jochen
J
Springer
Silvia
S
Amadesi
Marcello
M
Trevisani
Selena
S
Harrison
Q Thai
QT
Dinh
Gerald P
GP
McGregor
Axel
A
Fischer
Pierangelo
P
Geppetti
David A
DA
Groneberg
D000109:Acetylcholine / Q000494:pharmacology; D001980:Bronchi / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000737:chemistry / Q000502:physiology; D004848:Epithelium / Q000737:chemistry / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000737:chemistry; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009412:Nerve Fibers / Q000737:chemistry; D010446:Peptide Fragments / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000032:analysis
D010446:Peptide Fragments; D018015:Receptors, Calcitonin Gene-Related Peptide; C058636:calcitonin gene-related peptide (8-37); D010656:Phenylephrine; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin