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Epithelium integrity is crucial for the relaxant activity of brain natriuretic peptide in human isolated bronchi
Author(s) -
Matera Maria G.,
Calzetta Luigino,
Passeri Daniela,
Facciolo Francesco,
Rendina Erino A.,
Page Clive,
Cazzola Mario,
Orlandi Augusto
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01339.x
Subject(s) - epithelium , pharmacology , medicine , pathology
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.