Document Detail

Epithelium integrity is crucial for the relaxant activity of brain natriuretic peptide in human isolated bronchi.
MedLine Citation:
PMID:  21410689     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND PURPOSE Brain natriuretic peptide (BNP) plays an important role in several biological functions, including bronchial relaxation. Here, we have investigated the role of BNP and its cognate receptors in human bronchial tone. EXPERIMENTAL APPROACH Effects of BNP on responses to carbachol and histamine were evaluated in non-sensitized, passively sensitized, epithelium-intact or denuded isolated bronchi and in the presence of methoctramine, N(ω) -nitro-L-arginine methyl ester (L-NAME) and aminoguanidine. Natriuretic peptide receptors (NPRs) were investigated by immunohistochemistry, RT-PCR and real-time PCR. Release of NO and acetylcholine from bronchial tissues and cultured BEAS-2B bronchial epithelial cells was also investigated. KEY RESULTS BNP reduced contractions mediated by carbachol and histamine, with decreased E(max) (carbachol: 22.7 ± 4.7%; histamine: 59.3 ± 1.8%) and increased EC(50) (carbachol: control 3.33 ± 0.88 µM, BNP 100 ± 52.9 µM; histamine: control 16.7 ± 1.7 µM, BNP 90 ± 30.6 µM); BNP was ineffective in epithelium-denuded bronchi. Among NPRs, only atrial NPR (NPR1) transcripts were detected in bronchial tissue. Bronchial NPR1 immunoreactivity was detected in epithelium and inflammatory cells but faint or absent in airway smooth muscle cells. NPR1 transcripts in bronchi increased after incubation with BNP, but not after sensitization. Methoctramine and quinine abolished BNP-induced relaxant activity. The latter was associated with increased bronchial mRNA for NO synthase and NO release, inhibited by L-NAME and aminoguanidine. In vitro, BNP increased acetylcholine release from bronchial epithelial cells, whereas NO release was unchanged. CONCLUSIONS AND IMPLICATIONS Epithelial cells mediate the BNP-induced relaxant activity in human isolated bronchi.
Maria G Matera; Luigino Calzetta; Daniela Passeri; Francesco Facciolo; Erino A Rendina; Clive Page; Mario Cazzola; Augusto Orlandi
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  163     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-27     Completed Date:  2012-01-31     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1740-54     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Unit of Pharmacology, Department of Experimental Medicine, Second University of Naples, Naples, Italy.
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MeSH Terms
Acetylcholine / biosynthesis
Bronchi / cytology,  physiology*
Carbachol / pharmacology
Cell Culture Techniques
Cholinergic Agonists / pharmacology
Enzyme Inhibitors / pharmacology
Epithelial Cells / drug effects
Epithelium / drug effects*,  injuries,  physiology
Histamine / pharmacology
Histamine Agonists / pharmacology
Middle Aged
Muscle Tonus / drug effects
NG-Nitroarginine Methyl Ester / pharmacology
Natriuretic Peptide, Brain / physiology*
Nitric Oxide / biosynthesis
Nitric Oxide Synthase Type II / antagonists & inhibitors
Receptor, Muscarinic M2 / antagonists & inhibitors,  drug effects
Receptors, Atrial Natriuretic Factor / drug effects,  metabolism
Respiratory Hypersensitivity / chemically induced,  physiopathology
Reg. No./Substance:
0/Cholinergic Agonists; 0/Enzyme Inhibitors; 0/Histamine Agonists; 0/Receptor, Muscarinic M2; 10102-43-9/Nitric Oxide; 114471-18-0/Natriuretic Peptide, Brain; 50903-99-6/NG-Nitroarginine Methyl Ester; 51-45-6/Histamine; 51-83-2/Carbachol; 51-84-3/Acetylcholine; EC Oxide Synthase Type II; EC protein, rat; EC, Atrial Natriuretic Factor

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